WPI’s response to CROI was
“It is interesting that infectious XMRV is
still found only in human cells and not in mouse cells or mice. In addition,
these data have little to say about XMRV infection in humans.” In an email Dr.
Mikovits stated “There is still not one piece of evidence of contamination in
the Science paper. All of the authors stand by the conclusions and data in
Lombardi et al”.
Deckoff-Jones Talks – Dr. Mikovits was too busy to do an interview
but Dr. Deckoff-Jones got her two cents in her personal blog. She
asserted that because neither the WPI nor the Cleveland or the NCI labs in the
study have ever used the 22RV1 cell line their samples could not have been
contaminated by it. Indeed she reported that that “all three investigators at
different institutions can prove beyond a shadow of a doubt (that it – 22RV1
cell line) never entered their laboratories (personal communication)”.
Actually proving contamination has occurred
has always been the weak link in the contamination theorists logic chain. Thus
far the WPI has used none of the reagents, cell line, laboratory animals, etc.
that have been associated with contamination.
This is an interesting point given that the
central problem with XMRV has not been that it’s found too often -as one might
suspect if it was a lab escape – but that
it’s not been found enough. If XMRV is an escape from a lab why is it
showing up in a lab that seems to have so few links to possible sources of
contamination? Conversely, why is XMRV not showing up in other labs more
often? To date only the labs in the original study (and
VIP Dx) have been the only labs to find XMRV.
Garson and Tower’s analysis of Silverman’s
integration data suggested that Silverman’s prostate cancer samples may have
been contaminated but that data was inferential and we will surely hear more
from Silverman on that. Even if that’s so how did the virus get into Silverman’s
lab if it has not been using 22RVI and why has it not appeared elsewhere?
She also noted that inadvertent endogenous
retrovirus introduction into cell cultures and vaccines is nothing new and that
mouse cells have been used frequently in these processes and in gene therapy.
Essentially she seems to be saying XMRV…..a lab creation? Sure -why not? But why
assume that it took until 1999 for a recombinant event to create XMRV? Why not
much, much earlier?
She ends by suggesting that many
other recombinant retroviruses are possibly infecting humans around the world by
the same process and that it’s quite plausible that vaccines containing
infectious human retroviruses have going out for over 50 years. She then ties De
Freitas retrovirus in CFS to autism and suggests the CDC’s inability to
find it in 1993 may have caused the current epidemic of autism.
- Dr. Vernon on CROI – Dr. Vernon presented a step by step overview of the CROI papers. She ended up concluding that
the issues surrounding XMRV continued to grow rather than being resolved after the conference. She agreed the
“current evidence’ suggest that XMRV was created in the lab but that doesn’t mean the virus is
benign or is not associated with diseases and XMRV should continue to be the focus of study – and indeed
the conference presenters indicated it would be. Her endpoints are below.
“I agree that standardized, validated assays must be a priority for the field.
The discussion about ways in which XMRV behaves differently than other gammaretroviruses and
its ability to establish productive infection highlight the need for
continued disease association research. The list of important outstanding issues grew longer,
rather than shorter, after hearing these presentations. Even though the evidence indicates
XMRV evolved in a lab, that doesn’t imply that its current existence is benign.Darwin did not have the advantage of understanding how viruses contribute to the evolution
and adaptation of species. We now know that viruses are some of the most rapidly evolving
“species” on the planet. This seems to be a prime opportunity for scientists to put fractious
politics aside, consider all the facts and keep an open mind before concluding that there are
no diseases associated with XMRV.”
- Dr. Mikovits – reportedly penned an email to someone stating something to the effect that “we will prove XMRV is not
a contaminant”. An interview with her on the current state of XMR has been requested.
- Autism Study – Negative.
This study has been ‘out’ for awhile but just showed up in Pubmed. No XMRV was found in the blood, semen or
brains of about 100 people with Austism. The autism link to XMRV was announced early but this is the second study that has failed to find it
in people with autism. Alex on the PR Forums pointed out that the WPI looked at autistic individuals living in families where members had already
tested positive for XMRV and this study simply looked at people with autism
and they could be different cohorts. . (This could suggest XMRV could be present in some people with autism but not contribute to
autism in most people)
- XMRV Study Review – a review of published studies and past conference reports (as memory serves!) of disease groups looked at since the Science paper was published in Oct of 2009 presents a fairly bleak picture.
Of CFS studes 4 or 6 have been positive (depending on whether Alter/Lo’s/Hansen’s paper is put into the XMRV or MLV category) and 9 studies
have been negative. In prostate cancer we have two positives and 6 negatives (some of the negatives had extremely low
positive rates), HIV – 0 positive, 5 negative, Autism – 0 positive, 2 negative; Fibromyalgia – 0 positive and 2 negative,
immune compromised – 0 positive and 2 negative and multiple sclerosis/
/infectious diseases/arthritis – all 0 positive and 1 negative. (Since some studies
looked at multiple groups this overstates the number of studies.
Come Down At CROI – XMRV took its biggest shots yet the CROI retrovirology
conference. Researchers have been working their way a line of investigation that
culminated in a paper by Dr. Cingoz that purports that XMRV is a laboratory
derived virus that was accidentally created between 1996 and 1999 when prostate
cancer cells were grafted onto nude mice. Two endogenous retroviruses in the
nude mice have been identified that are believed to have ‘recombined’ to form
the complete XMRV virus. From there the thinking is apparently that XMRV
spread from lab to lab and somehow found it’s way into the WPI’s samples XMRV is a live virus that
can readily infect tissues in the lab but it’s fate as a human infectious
pathogen is unclear.
The evidence is still circumstantial and
there’s no direct evidence proving contamination of the WPI’s samples. Instead
there’s a logical and a
short comment reportedly from Dr. Mikovits clearly indicated she was not buying
it, but the prevailing
opinion, at least at this conference, was clearly that XMRV found its way
(somehow) into the WPI’s and others samples and never actually infected the
patients. It appears that our perennial fence-sitter. Dr. Coffin is not sitting
on the fence anymore. His lab has been heavily involved in digging into the
contamination issue and with the latest study seemingly putting all the pieces
together, he appears to be satisfied with the majority opinion.
More News – Spain was well
represented with three papers. One group found no XMRV in HIV patients, another
looked at over 1100 CFS, FM, HIV, hepatitis and other patients and found 0%
antibodies (Abbott) or or positive PCR resultsfrom the CFS patients. They
did find 6% positive results from the cancer
patients but only from one gene and no antibody tests were positive.The
irsiCaixa lab many had pinned their hopes on did find XMRV growing in a small
number of EBV transformed cell lines, which was something, but the current focus
on contamination in cell lines the effect of that finding was blunted. p Dr.
Mikovits has questioned whether the IAP contamination test might falsely identify XMRV as a contaminant
but that did not happen in the B-cell study; the IAP test showed no contaminants
in the positive B-cell lines.
A German lab found no XMRV in 500 samples from transplant patients.
The Positive Patient ReTest Tests–
As they concentrate their efforts to find XMRV researchers are now looking in
patient that tested positive in the past – presumably by the WPI. Dr. Joliceur,
Dr. Miller and Dr. Maldarelli have all at least started studies employing this
kind of protocol. At the conference we heard of two more small efforts. (Of
course this appears to be the central protocol of the BWG study; it involves
getting a fairly large number of patients that tested positive for XMRV by the
WPI, throwing in a number of certified negative controls and then determining if
the WPI and the other labs can pick out the patients identified as having an
New Test – Same Result
– The NCI funded Kearny study (with Malderelli and Coffin and the Blood XMRV Sci
Res Working Group) reported they have developed a ‘single copy’ assay (X-SCA)
that can differentiate between XMRV and MLV’s. Dr. Kearny warned that simply
cutting 300 nucleotides from the end of one of the sequences would result in
researchers misidentifying a MLV (mouse contaminant) as XMRV. Importantly
they validated their test using the macaques infected with XMRV. She
demonstrated that the X-SCA test was able to pick up the virus in immune blood
cells of the macaques throughout their (admittedly brief) lifespan. When she
turned to four patient previously identified as having XMRV, however, she was
unable to find XMRV. She also tested 134 patients with prostate cancer and
found no XMRV.
Henrich had not been able to find XMRV in CFS and in
other patients with immune dysregulation in the big Mass study. Now he looked for XMRV in two previously positive patients and
did find an MLV sequence that was 90% similar to that found in the Alter/Lo
trial but concluded it was a contaminant.
Missing Advocates – Some of XMRV’s chief advocates (Dr. Mikovits, Dr. Ruscetti, Dr.
Silverman, Dr. Singh, Dr. Alter, Dr. Lo) who would have presented a different
viewpoint did not present at the conference. We’re also, of course, still waiting
on studies from Dr. Lipkin, Glaxo-Smith Kline and Dr. Singh and of course, the
all important Blood Working Group tests. It’s hard to imagine that the
double-blinded BWG tests will not either turn the field around for XMRV or
essentially end it. If the WPI can pick out the positive samples from the
negative samples; ie show that the bug is there and they can find – then one
imagines the research community will come roaring back.
Tomorrow, the key culprit at CROI – the 22RVI cell line and why it’s
playing such a big role plus the CDC finds XMRV….. in its lab workers? and
- CROI is Here!
– the big Retrovirology Conference CROI has begun and we have the entire lineup and (contrary to past
reports) it has a full XMRV slate. The XMRV presentations will take place on March 2nd, the last day of the Conference.
They cover a variety of aspects; researchers continue to refine their ability to
find the virus with one study focusing on a new cell line developed to detect it
and the development of a new assay by NCI researcher Mary Kearny. The irsiCaixa
lab in Spain that appeared to have found the virus appear to indicate they can
infect lymphoid cells with it and that they have found B-cells infected with
XMRV. The later study would be the more important one since if my interpretation
of the title is correct, it could
indicate they found it in blood samples.
The meaning of Henrich’s talk
“Discordant XMRV Test Results and Non-reproducible Mouse Endogenous Retroviral Detection in an XMRV Prevalence Study” – is definitely
is anybody’s guess. He did the Harvard study last year that failed to find
XMRV in several hundred HIV, rheumatoid arthritis and CFS patients. Dr. Switzer of the CDC will
apparently talk on the CDC/Cooperative Diagnostic study that failed to find XMRV using a variety of PCR
and antibody tests in CFS patients across the country. Interestingly, he will also give a talk on
‘Extensive Genetic Recombination in the XMRV Genome” Genetic recombination occurs when genes in paired
chromosomes switch places. His talk certainly indicates researchers continue to dive deep in XMRV.
Hue, the geneticist, who found that the XMRV believed found in humans was basically identical to a strain produced in the lab
by the 22RV1 cell line, will
report that XMRV is caused by laboratory contamination. Since Hue’s paper appeared some time ago it appears
he has some new information to report. The last talk will assert that XMRV came from an endogenous
murine leukemia retrovirus, which would be interesting, but would not, I wouldn’t think mean anything about
XMRV’s provenance in humans. My guess is that it doesn’t matter where XMRV ultimately came
from – what matters is where the XMRV in the blood samples and prostate samples of humans came from. If they came from an
infected human cell then XMRV is in good shape, if they came from the 22RV1 cell line
-as Hue asserts – then XMRV is
in real trouble.
This is why the issue of XMRV integration has become so important. An integration study that
indicated XMRV DNA was surrouned by human DNA would indicate that infection had occurred. One that indicated
that XMRV DNA was surrounded by say, mouse DNA would indicate otherwise. A
recent study suggested XMRV was not integrated into human DNA but it was not
definitive. Dr. Silverman, one of the co-authors of the Science paper, is
reportedly looking at XMRV integration. A report on the Forums from someone who
says he has an inside source states Dr. Silverman is not finding XMRV
integration into human cells but Dr. Silverman is not at this point scheduled to
speak at the conference – so that is decidedly anecdotal information.
- Dr. Mikovits to Talk – Dr.
Mikovits will talk on March 17th at the University of Alberta in the new
La Ka Shing Institute of Virology on “Strategies for Detecting XMRV in
Clinical Samples”. This is an interesting location to hold this talk
because the Univ. of Alberta reported in early summer of last year they were
collaborating with the WPI to look for XMRV in CFS patients. They anticipated
they would be done in a couple of months – and that was the last time we heard
of them. Now Dr. Mikovits is talking on how to find XMRV there. Have Univ of
Alberta researchers found the virus?
- Two More Negative Studies – it’s almost beginning to sound like a broken record but two more negative
studies have come out.
A Cooperative Diagnostics/CDC study came out that used severely ill CFS
patients from across the country and multiple PCR tests, including those used by the Lombardi group, which were
more sensitive than ever plus antibody tests prepared using the ‘wild virus’ which worked perfectly in the
infected macaques….and found nothing at all in the CFS patients. An
interview iwth the author is in the works.
Another study from the
Wellcome Trust Group that did the genetic analysis of XMRV in the Hue paper
indirectly suggested that the prostate cancer studies are from a
contaminant. They didn’t provide proof but their findings suggested that might
The PCR Question! – there’s a really good article in BioTechniques.com on
the role PCR should or should not play play in figuring out XMRV and
appears to cover all sides of the issue. It shows how tricky everything is…it
mentions the great lengths the WPI went to ensure that no contamination occurred
but then notes that with such rare viruses researchers have to increase their
PCR sensitivity which makes them more susceptible to mouse DNA contamination. On
the other hand Dr. Mikovits referred to the extensive tests on controls that
have not shown contamination in them but have shown evidence of the virus in
patients. Another researcher said you have to overthrow an entire field of
Science if you were not to trust the PCR results. There is still no easy answer.
The article is called “Walking on Eggshells, PCR assays for XMRV detection”.
- People with CFS Locked out of Alter/Lo Videocast
– Without warning or
explanation the NIH decided to allow only people associated with the NIH to
watch the Alter/Lo videocast on “Is there a Virus in CFS” disappointing many
people who had planned their day around it. My understanding was that the event
was open to all. On Jan 26th the CAA
reported that the videocast was free and open to the public and no registration
was required as well. Clicking on the link today, however, brought a title
stating (NIH Only) which meant that only computers in the NIH network or with a
special PIN could view it. 116 people were watching the videocast shortly after
According to the FAQ’s the program should be archived in a few days and then presumably
will be available to all. The NIH has a YouTube site where about 50 video’s are currently posted.
- XMRV in New Zealand – there don’t appear to be any XMRV studies in New Zealand but
they are preparing the ground. ANZMES has provided Dr. Warren Tate, the Associate Dean of
Research at the Universit of Otago, with the funds to collect and catalogue
blood samples (ie create their own Biobank). Once the validated assays are
present they hope to look for immune biomarkers as well and they can use the blood samples to quickly attempt to validate significant
research findings as they arise. They are building a foundation for success :). (Thanks to Heather
for the info) From Doctor Tate:
“I thought the
research paper published in Science was exquisite. Left open was a
major question however; was this an opportunistic virus that had
colonised a defective immune system perhaps sustaining an illness
initiated by another cause (virus or different microbe, or
environmental toxin), or was it the primary cause of the illness?
Scientists are in heated debate about this today-the answer is that we
just do not know at present.Although several groups in the United Kingdom and Europe, as well as the Centre
for Disease Control (CDC) in the US reported they could not find XMRV in patient
cohorts, in the last 2-3 months there have been several new reports of the virus
having been found CFS patient samples in both US and Europe. Nancy Klimas
indicated in her recent visit to New Zealand that the different research groups
are finally talking with each other and consensus techniques for collecting
blood samples, and for detecting the virus will emerge soon.
How can those affected with ME/CFS here in New Zealand benefit from
this? At present we do not have a carefully catalogued sample
collection from patients that is suitable for comprehensive study, not
only to screen for XMRV, but also for analysing DNA polymorphisms
(specific variations), for doing gene screens, and for studying
ANZMES has provided the support to me to establish
this, for which I am very grateful. That in my view is the first
essential step, but must be done carefully so the bloods have validity
for a predicted wide range of future studies. My research group is
developing molecular tools that might be suitable for a set of
diagnostic biomarkers focussing on molecular changes in ME/CFS in the
innate immune pathway against viruses. We hope to access the tools for
screening for XMRV when the blood sampling and detection consensus is
settled. It is my goal that we can have a research and patient based
focus for ME/CFS in New Zealand that can rapidly respond to new
international findings as they arise.”
- Alter/Lo Videocast
– This 2 hour (!) live
videocast from two of the most forefront proponents of XMRV could be really
something. Dr’s. Alter and Lo will be talking on Is There a Virus
in CFS? on Feb 22nd. It starts at 4pm EST /1 pm PST.
Check it out here.
Dr. Bell Will Talk on
- Lo/Alter/Gill Slides for “Is there a Virus in CFS” talk on the 22nd are up.
Lo’s here and Gill’s (well you might not want to check out Gill’s :))
“A Persistent Chronic Infection” – in Amy Dockser Marcus’s latest blog on the Macaque study she quotes Dr. Silverman as saying
its clear that “The virus causes chronic, persistent infection” and notes that the study clearly shows the virus
can be difficult to find in the blood – even after its taken root in numerous organs of the body. They also noted that
Abbott labs funded the study (at $50,000 an animal) as part of its effort to develop (antibody) tests for XMRV. The publication of
the Macaque study has been a nice win for XMRV after some tough times. It doesn’t explain why
other labs have been unable to find XMRV when the WPI was (patient cohort?) but it does clearly indicate how hard it can be to find the virus in the
blood even when it’s present in numerous organs. Check out the Racaniello blog below for more.
- Dr. Raccaniello Takes A Look at the Recent Macaque Study
Published – among other things he noted the wide variety of tissues
effected including spleen, lymph nodes, the lining of the gastrointestinal
tract, prostate, testis, cervix, vagina, and pancreas, but not in others
including brain, heart, kidney, and bladder and that XMRV showed up in the
prostate early. The concentration of XMRV in the reproductive tissues (testis,
cervix, vagina) suggests it may be transmitted sexually. He noted that the
virus levels plummet after the acute infection but that immunocompromised
individuals may show a different pattern (increased levels of virus?). He also
noted that the authors stated that if XMRV causes CFS or prostate cancer the
link would be a ‘temporally distant one” which just seems to suggest that it
looks like it would take a substantial amount of time to do its mischief. He stated that in
interpreting the results of animal studies, we must keep in mind the adage, ‘Mice lie, monkeys exaggerate‘. We also learned that each
monkey costs $50,000!
Question session – the questions were the most interesting
part of the blog.
In response to a question about looking for XMRV in human tissues he felt that the study should prompt
research into that: “this
work should stimulate research into understanding where XMRV can be found in humans”. One interesting question notes that the
investigators were able to ‘re-activate the virus by stimulating the virus and
asks why not do that in humans? Or why not simply have people with CFS exercise
and see what happens?Look in the organs – Dr. Raccaniello clearly felt the study explained why XMRV
might be so difficult to detect in humans and thought researchers should start
looking in the organs. “You are right, from the results of this study it is
clear that we should be looking for XMRV in other organs, rather than blood. As the authors
write, if XMRV is involved in CFS and PC, the infection probably occurred some
time before disease. And the findings do suggest why the virus is difficult to
detect in the blood. Even proviral DNA was not detected, although in at least
one monkey it was still present.
No need to kill cells to cause damage – to a question of how XMRV could cause damage if it’s not killing cells
Dr. Racaniello replied – actually there are a number of ways: “Many viruses are noncytopathic in cell culture, yet cause disease in
humans. The tissue/organ damage is believed to be a consequence of
immunopathology – the immune response damages cells and tissues. There
is experimental support for this mechanism of pathogenesis for a
number of human viral diseases. See
- Spanish XMRV Researchers to Speak at
CROI – The Irsi Caixa team that appeared to be able to find XMRV last year
are reported to be giving a presentation with the intriguing title “XMRV:
New Findings and Controversies” at the big CROI Conference
(Conference on Retroviruses and Opportunistic Infections) in Boston from just a
week from now (Feb 27th-March 2nd). CROI did videotape all their presentations
These conferences will probably be good indication of
current interest in XMRV as researchers often present the results of
ongoing studies in them. It’ll be interesting, as we go through the year, to see how
much XMRV shows up at the conferences one year later. In early 2010 XMRV was a pretty hot item; just
a couple months after the release of the paper there were seven XMRV presentations
including one plenary session at CROI. In 2011 XMRV has one presentation and one
abstract devoted to it (that I could find :))
- Video’s of Annette Whittemore’s and Dr. Mikovits Talk at Gordon Medical Associates are Up
– the full video’s of the talks are up. XMRV Global Action is organizing a
transcription team to get them into print.
Check that out here.
- The Other Spanish
XMRV Study Stalled – we had a negative FM study come out of Spain but a
preliminary study that appeared like it might have some positive results,
unfortunately, is stalled for funds and could use some help.
Check it out here.
In ME Conference in May 20th in London – will feature a bevy of
interesting speakers including Annette Whittemore, Dr. Mikovits, Dr. Bell, Dr.
Montoya, Dr. Chia and Prof Mella (Rituximab) with more to come.
- Spanish FM XMRV Study – zero results. What to say except that this is another zero result study. This was not the
Spanish group, however, that reported they had found XMRV earlier.
- Dr. Mikovits on looking for a Human Tissue XMRV Reservoir
– Mya Simmons asked
Dr. Mikovits about exploring a human tissue for XMRV. Dr. Mikovits replied that
yes, they are interested in doing that but that a ‘political climate’ devoted to denying XMRV’s existence in humans was making
getting that done difficult.
“It has been detected in the prostate and in the monkey studies in ovaries,
spleen lymph nodes and kidneys. More extensive types of such studies are being planned by the WPI which is applying for human assurance protocol to create a tissue repository to do just that. The difficulty in doing such studies is the political climate trying to deny that XMRV, a new human retrovirus of unknown
pathogenic potential, is circulating through the human population.”
- XMRV Webcast Featuring
Dr. Kleinman – Is XMRV and Related Retroviruses: Are these a threat to
blood safety? – Dr. Kleinman is a Canadian expert in Blood Safety – one
forum member called this a ‘must see’. This guy can really talk and he really
lays out how severe CFS is and talks about the immune abnormalities.
- Dr. Deckoff-Jones Talks
– The XMRV finding has put the spotlight for the past year on the research side of the WPI (or the Center for Neuro-immune Disease) but that’s just half of the equation. When the Clinical side of the Center opens sometime in May
it will bring an entire new entity to the ME/CFS Community…an integrated clinic/research facility.
In this interview Dr. Deckoff-Jones talks about other the side of the WPI – the Clinic side. We find
out how large it is (it’s quite large!), what they hope to accomplish (quite a bit), how they plan to do it and how she hopes
it will change the face of CFS treatment.
Dr. McClure Resigns from CFS Grant Review Panel – The CFS SEP or Dr. McClure
or someone was apparently unprepared for the strong response from the patient
community as she stepped down from the post on Sunday. One wonders how often, if
ever, patient activity has prompted a change in membership in a grant review
panel for the NIH. (One wonders how many patient groups (a) know of grant review
panels and/or (b) actually take action to try to remove members. In any case,
Dr. McClure is gone and her replacement has not been, to my knowledge, announced
Twiv Broadcast with Dr. Racaniello and NYTimes journalist David Tuller discuss
XMRV and CFS – check out what’s been described as a thought-provoking
discussion. CFS apparently shows up about the 20 minute mark.
- Malderelli Study – the Malderelli XMRV retest study has elicited a
‘little’ controversy…:). Dr. Malderelli,
in a discussion with a patient, said he was collaborating with the WPI. Dr. Mikovits, however, in several emails
posted on the internet, has said neither the WPI nor Drs. Alter/Lo are or ever have collaborated with Dr. Malderelli.
Dr. Mikovits also wants patients to know that the Malderilli study will take
place in Dr. Coffin’s lab. From an email to a patient “She also informed me that the retesting of XMRV positive people is
set to take place in John Coffin’ s laboratory and that Dr. Malderalli works for John Coffin.”
IAP Test – there was quite a push to have researchers employ the
IAP test in their studies after the Retrovirology papers came out. The
controversy over what type of contamination test makes one wonder what, if
anything, researchers in this field can agree on. It’s almost one thing after
another (XMRV vs XMLV’s, VP62 vs wild type, contamination test, PCR vs
culturing, freezing/refreezing samples, test tube types, patient cohorts,….).
At the Workshop both sides (pro mtDNA, pro IAP) somehow not only proclaimed that
their test was more sensitive but that it was much more sensitive.
One thing is very clear, though, Dr. Mikovits does not support using the IAP test
in XMRV retest studies, eg; “The WPI will not recommend any XMRV positive patient participate in any study that uses the IAP assay ..it is not validated..never has been.”
Of course, the offsetting problem is that these other researchers don’t trust
the mtDNA test!…So now not only is there no consensus on how to find XMRV;
there’s no consensus on how to test for contamination…..
Dr. Mikovits has laid out her concerns in this area. Earlier she pointed to the paper and
presentation that concerned her. The ball, now, is really in the other researchers court;
it’s time for them to respond
to her concerns. Hopefully they will do so publically.
- Alter/Lo Videocast in About Two Weeks
– keep this on the calendar. Except for the Miller/Malderilli
controversy the XMRV beat has been pretty dead lately but this 2 hour (!) live
videocast from two of the most forefront proponents of XMRV could be really
something. Dr’s. Alter and Lo will be talking on Is There a Virus
in CFS? on Feb 22nd.
Check it out here.
- Indy Star Article on CFS and XMRV nice article on CFS and XMRV. Dr. Bells notes that if XMRV is it in
CFS–we’ve got it licked…which may not be, at least in the long term, too optimistic given the success seen with HIV – a much more complex retrovirus.
- NIH ME/CFS Grant Review Panel (CFS SEP) Takes a Step Back
– this is probably old news for many but
the seating of the Feb grant review panel for CFS at the NIH drew
no cheers. Yes, there were more researchers with CFS experience than on most of the
CFS SEP’s but that’s not saying much. Pain researchers dominated the panel (twice as many as
CFS) and we lost some strong pro CFS voices (Klimas, Ruscetti, Broderick). What
really got everyones attention, though, was the presence of
Dr. McClure – who has been very clear that she believes XMRV does not exist. She is one of the
two retrovirologists on the panel which means she will be reviewing any XMRV grant applications….not a pretty picture.
Protests quickly sprung up;
check out more on this situation here.
– This US NAIAD study
used VIP Dx Labs to look for XMRV in blinded CSF samples using both straight PCR
and culture. It failed to find XMRV using.
This was quite a promising study and it’s
the second NIH funded study in the last month to use cutting edge technology to
take a broad search for pathogens in the blood or spinal fluid that came up zip.
Their hope was
“The discovery of potential pathogens in cerebrospinal fluid of CFS would be
field-altering in terms of approach to the study of the disease and possible
early detection, prevention and treatment. This could be the gateway step to
generate new hypotheses and begin investigation into a microbe’s causal
association and ways to prevent (egg vaccine) or counteract the effects of a
It was an enticing vision but it was not to
be. Bear in mind that it was cutting edge technology and that can cut both ways.
- WPI Clinic Revealed
– Dr. Deckoff-Jones, in her latest series blog, has been laying out how the Clinic is going to
function..First the opening date for the
WPI is looking like May – just four months from now. God bless her, she’s making the money side of the Clinic very clear. When was the
last time any clinic spelled out why it was doing regarding money and treatment? She’s clearly very well versed in the how-to’s of clinic management.
First there’s the Medicare issue. The WPI just cannot
afford to accept Medicare. (My experience is that very few CFS doctors accept insurance let alone Medicare). Medicare is apparently great for
covering big operations and 20 minute visits but it sucks at covering 1 1/2 visits and complicated diseases.
She said ” Also accepting Medicare/Medicaid is an all or nothing proposition. You have to play completely by their rules or opt out all together. They don’t allow a middle ground. The government thinks a 20 minute visit is adequate,
particularly since there is no treatment.”
No insurance – no insurance either and personally I would have been surprised if they had. The last ME/CFS doctor I saw that
took insurance was about 20 years ago…it just doesn’t seem to be done anymore. The Clinic simply doesn’t have any money to
burn through while they wait for insurance payments to kick in – it must start paying for itself immediately – or it won’t open – it’s as simple
Some Pro-bono Treatments – she did note that they will be providing pro bono treatments to a percentage of
patients…(Some of our wealthier doctors could take a hint)..and they will determine the percentage as the clinic opens and as they
figure out where they are financially. One has the feeling that Annette’s fingerprints are all over this…..it’s about helping
as many people as possible given the monetary restraints of operating a medical clinic.
Dr. Deckoff-Jones has been through the
money grind at expensive, profit oriented clinics and stated
I am determined not to do that to others. I hereby promise that nobody is going to get rich on the budget I’m putting together. Salaries will be fair, but we are looking for people for whom it is more than a job. The purpose of the clinic is to treat individual patients, but because of the translational medical approach that will be engendered by existing
in concert with the research lab, there is a bigger purpose as well... This was “I hereby promise that nobody is going to get rich on the budget I’m putting together.”
was music to my ears. There certainly are many ME/CFS physicians who could be
doing much better working outside of CFS – the work is a labor of love for them as well and Dr. Bateman, who lost her sister to CFS, springs immediately
The Clinic itself sounds very impressive. Alot of people will want to be seen – and it’s built to see alot of people.
“As for whether the WPI should have a clinic that treats a volume of patients, or just be doing a few clinical trials, that decision has already been made. Annette Whittemore’s vision of translational medicine included treating patients from the beginning. Bench to bedside to bench. The clinic exists. It is a very large space, capable of seeing a large volume of patients.
There are many patients asking to be seen.”
The Director! – Dr. Deckoff-Jones will be the “Director of Clinical Services for
the WPI” (actually called the Center for Neuro-immune Disease” and is recruiting
Physicians, nurses, PA’s and a practice manager.
What shines through in the blogs
Dr. Deckoff-Jones posted is a commitment to
communication and transparency. The WPI clinic will not be a miracle worker
necessarily; what it will be able to do is systematically and methodically
analyse the different treatments available and integrate them with cutting
edge research. Nobody is doing anything but suggesting that there isn’t a long
way to go but the WPI’s blend of integrated research/treatment should help move
the field much faster. Would that there were more Centers out there. There’s
alot more in these blogs. Check them
- GMCaF er GCmaF er GCMaf – whatever it is Dr. De Meirleir is using this immune factor extensively and several people
have recently returned from his clinic to tell the tale…and it’s interesting to hear not just how they are doing –
but Dr. DeMeirleir’s thoughts on treatment. Some people are improving and some are not. GCMaF is not an antiviral but it might
be able to enable the body to better fight viruses. Check
out the thread here and pick up some
of the latest information
on how one of our most experienced physicians is using this new treatment – which is not available in the US.
- Another Antiretroviral trial starts -pinkytuscadero has been bedridden for most of the past 24 years!!!! She has tried just about
everything and nothing has really helped – a heart breaking story….Now she is starting out, under the care of her physician,
with tenofovir and raltegavir (no AZT – her doctor thinks those two drugs are enough and AZT is harder on the body). Everybody wish
her the best of luck…
On a interesting side note – at one point Ann mentioned
that during a visit to an HIV doctor Dr. Mikovits statement that immune factors
like Ampligen and GCMaF might actually stimulate XMRV to replicate and leave the cell. He said that’s exactly what they
are trying to do with HIV! THey are trying activate HIV as much as possible so they can track it down and kill…
HIV hides in its latent state and then later reactivates. If they can get it to reactivate all at once apparently they
feel they have a chance of wiping it out completely – at least that’s the theory. They are nothing if not clever.
– meanwhile Daffodil, who has been on ARV’s for a solid 10 months with
little discernible improvement has had a much better last couple of weeks. Could
it be that they are finally kicking in? She actually reduced her dose of AZT by a 100
- NIH Videocast on Viruses and CFS Featuring Lo and Alter!
– Now this will be interesting. Dr. Lo/Alter have presumably been
working away for the last 3 months or so at either showing XMLV integration into human DNA in their samples or at isolating
the virus itself. In about 3 1/2 weeks they’ll be giving a 2 hour lecture called “Demystifying
CFS – Is there a Virus”. That’s a long lecture and who knows what come of it. This lecture will be
technical – it’s directed towards Ph.D students and program managers but it’s open to everybody.
Check it out here
- Arizona Lab Says Yes to XMRV?
– JohnnyD on the PR Forums dug up a statement from diagnostic and research lab in
Scottsdale, Arizona called Fry Labs – that yes, they are finding XMRV/XMLV’s. Fry appears to specialize in
tick borne and other parasites and bacteria. XMRV appears to be the only virus, let alone retrovirus, they
are looking for.
They present a nicely written, well documented paper altho their grammar isn’t too spectacular – check out this sentence in which
two misspelled words in this sentence (provial instead of proviral, our instead of for) “Fry Laboratories offers our research use PCR assay for licensed clinicians and health care professionals that
specifically detects two different loci of these related provial genomes.”
They are sequencing everything they find and
appear to be finding more XMLV’s than XMRV…and they appear to be finding them in levels similar to those Lot/Alter
found in health controls; they state Any positive result from either region is followed up with direct sequencing and analysis.
Fry Laboratories is in approximate agreement with an NIH study  where approximately 7.7% of
an unselected population displaying detectable levels of murine leukemia viruses (MLV) related proviruses.
We have sequenced fragments of these patient-derived genomes and have discovered novel variants of the XMRV and MLV-related viruses
beyond what is published in the literature.”
Some digging from a
found a blog which has some questions about the lab and stated it is
run by a single general practitioner who is not a board certified laboratory
pathologist. There are definitely some warning signs; it’s a small lab – that is not
experienced with retroviruses (or viruses) – that is finding new variants that
other larger, more sophisticated and experienced labs have not been able to
find…it’s something to be careful about.
They are offering the XMRV test for physicians.
American Red Cross Moves Forward Quickly! – Amy Dockser’s latest health
blog from the WSJ is really interesting. First of all it states that the Red
Cross is starting to collect samples from no less than 10,000 donors to search
for XMRV and XMLV’s. Another study will look at,120 people have already received
blood. The tests will be run by Gen-Probe and Abbott labs.
Abbott, of course, is a huge diagnostic lab that has been
developing antibody and presumably other tests for XMRV. They have been closely
involved in XMRV for quite some time. They co-sponsored, with the NIH, the
International Workshop on XMRV in Sept of last year and Dr. Silverman is a paid
consultant to the lab. They were involved in the primate study that evoked so
much interest but an earlier Abbot antibody study found almost no XMRV in
about 1,000 healthy donors. Gen Probe on the other hand said in Nov that it had developed a
super sensitive test that could pick up XMRV before antibodies to it were formed.
Both studies are in the planning stages but sample collection will start soon.
One wonders when testing will begin…It appears we’re at least 6 months from
any BWG conclusions about standardized assays…Will Abbott be using the same
antibody test they used before? (And why do another test when Abbott’s initial
testing of about 1,000 samples was basically negative?) Will Gen Probe wait for the BWG findings??? Has the Red Cross –
which also is not part of the BWG, decided that the Abbott and Gen Probe tests
are accurate? It appears so.
- Dr. Mikovits Talks – Part II – we now have two accounts of
Dr. Mikovits talk.
has finished up her account and
has provided her overview as well. As often happens both contain bits the
other does not. Paula reported Dr. Mikovits said that 30% of adolescents
who have tested positive for XMRV will go on to develop a severe case of infectious mononucleosis (glandular fever in some
countries) and will not recover; ie will go on to develop CFS. Dr. Mikovits also reports that, while ARV’s have not been the
silver bullet hoped for, that as patients on them do improve a bit – antibodies to XMRV start showing up – indicating that
their immune functioning has improved. Most people on ARV’s, however, have not improved. If you’ve improved on Rich Van Konynenburg’s methylation protocol – you’ll probably
be happy to see it recommended and others might want to give this pretty unexpensive option a try.
The WPI has found two
variants of XMRV – one
of which, if I got it right, is similar to the pMLV’s Alter found. Retesting has shown that about 30& of XMRV positive patients
have both. The list of diseases XMRV has been found in has grown and grown and now includes FM, Lupus, Lyme disease (very
strongly), peripheral neuropathy, autonomic neuropathy, some lymphomas, MS, Parkinson’s, ALS, dementia….This report appeared to
come from a medical practice that is testing its ‘neuro-immune patients’ but apparently not others so there is no information on
it prevalence in non neuro-immune disorders. The most exciting statement was Dr. Mikovits statement that with regard the second-guessing that
she ‘expects the politics will go away shortly’ which suggests some big news might be in store in the near future.
GcMaF Results – iLannie reported that in her talk Dr. Mikovits noted that
GcMaF- a substance that is apparently not available in the US but which
Dr. De Meirlier is using in his XMRV positive patients – might be able to get at
XMRV reservoirs. Rivka is compiling a list of people on GcMaF and their results
thus far….she has about 10 people and four results; one excellent, one
mild and two no response. If you’re taking it you
can tell her how you’re doing here.
- Mindy Kitei Investigates GcMaF– Mindy
Kitei noted that Dr. Meirleir reports that 80% of his patients feel
significantly better on GcMAF and Nexavir digs into whether some SNP’s play a
role in who responds. Just below that post is another post exploring the ins and
outs of this issue.
- GcMAF poll
– if you’re trying GcMAF for XMRV please take the poll
- Dr. Mikovits and Annette Whittemore
Talk in Santa Rosa – Lannie has provided a nice overview of the first part of Dr. Mikovits, er Annette
Whittemore’s talk (Annette had to step in for a bit when Dr. Mikovits plane was delayed). The dangers of sample freezing were
mentioned again….could such a simple (but perhaps overlooked) factor be causing the negative results? We also heard that
XMRV infection rates in families seem to be evenly split between men and women and a closer look at those original
samples found a second strain of XMRV in about 30% of them. For more check out the overview
- The Canada Studies – a Key Figure Shows Up? – in the look at
the year ahead in CFS a set of very interesting Canadian XMRV Studies were
missed. These studies, done in full communication with the WPI, were started
last July and involve Dr.
Stein, Dr. Tyrrell and Dr. Houghton at the University of Alberta.
is an intriguing figure. He was nominated for the CFSAC panel last year by the CFIDS Association of
America and was accepted. He kind of snuck in under the ME/CFS Community’s radar
but he may be the most celebrated researcher yet to serve on the panel. A former
Lasker award winner for the discovery of hepatitis he was described in this way
by the Pres. of the Univ. of Alberta.
He has no background at all
and Kim McCleary was pleasantly surprised he accepted their offer. He was quite
intrigued by EBV connection at Science Day and clearly touched by some of the
stories and openly talked about wanting to
get the pharmaceutical industry involved in a study. In the past year he
received the Canadian Excellence Chair for Virology and he joined the newly established
Li Ka Shing Institute of Virology which received $75
million dollars in grants at the University of Alberta. In his interview he
talked about doing three things; two involved hepatitis C (170 million people
around the world are infected) and the last was uncovering new viruses at play in diseases.
No mention was made of CFS or XMRV but he is involved in the Alberta XMRV
studies. In any case, connections do matter and one wonders if Dr. Houghton
might have gotten connected to CFS at a very opportune time.
His presence at the
CFSAC panel is an illustration of the increasing prominence of many of the
members. With Dr. Lipkin, Dr. Singh, Dr. Holmberg and an HIV head at the Univ.
of Pittsburg all nominated to the panel (by the CAA – no other nominations are
known, if any were received) hopefully more major figures will soon be joining
Wellcome Trust Researchers Respond to Criticisms – that they went too far in their conclusions by
stating that they believe that they did not, that they believe that ‘patient-derived XMRV’ contains
too little sequence variation for it to be a human pathogen, etc.
Dr. Mikovits Clears Up Reported Conversation On Anti-Retroviral Success – A
report bounced around the Internet of a conversation with Dr. Mikovits in which
she stated high rates of antiretroviral success with XMRV infected patients. In
a statement provided by Dr. Deckoff Dr. Mikovits reported that while some
successes had been the seen the report was much too optimistic.
Dr. Racaniello on Why Anti-Retrovirals Might Not Work With XMRV – and hence
why limited success with ARV’s doesn’t mean much about XMRV in humans…..the
general jist is that if the ARV’s stop viral replication -and the virus is doing
its damage by replicating then you’re in good shape…but if it’s doing it
damage some other way – then, you’re not….and nobody knows how XMRV does what
damage it may be doing.
- CFIDS Association Decries Media Dedicated to Sound Bites and Suggests “We’ve
Only Just Begun” Understanding XMRV – In her letter from the CEO’s desk
letter “Headway, Headlines and Healthy Skepticism” for January Kim McCleary took the media to task for not using source
documents and stated that vital XMRV studies were unaffected by the media blast
(largely begun in the UK). Besides the ‘Big Two” (Lipkin and BWG) she stated
other researchers were continuing their efforts unabated and that they would
incorporate the study findings into their efforts….. something Dr. Bateman
eluded to in her earlier webinar.
Reaching back 20 years she also noted that CFS was associated with three
different possible retroviruses over six years in the early 1990’s and many
people thought those investigations ended early. Of course, science is much more sophisticated
now and more resources are being devoted to XMRV. In any case Kim McCleary’s and
Dr. Komaroff’s warning that it will take multiple studies to prove anything pointed out
the fact that even if Dr. Lipkin finds XMRV in six months – that finding will
have to be validated by more studies for a consensus to occur….The complete
story on XMRV will take some time to unwind no matter how it turns out.
The BWG Transcripts Intrigue – the full transcripts of the
BWG meeting are available and contained some real shockers.
The Craziness of it All – Lo/Alter and the IAP test – this is the stuff that makes patients and, no doubt, researchers
crazy. If anything seemed clear after at the Retrovirology papers it was that the consensus was that if you’re going to
search for mouse DNA – that IAP test was the one to use – not the mtDNA test used by
WPI and Lo/Alter. The talking heads on the Twiv broadcast, in fact, (if memory
serves) suggested that Lo/Alter go back an retest their results with the ‘more sensitive’ IAP test.
The transcripts indicate, though (thanks Biophile), that at two points during the Workshop Alter noted they
did use the IAP assay and that it was
actually ‘much’ less sensitive that the mtDNA assay the other researchers were turning their noses up at
– some of them found it was less sensitive than the mtDNA test….which brings
up the question that everybody must have in the backs of their minds after all
this – Is there anything retrovirologists cannot disagree on?
Like Fish in Water – Mark pointed out that the ‘recovered patients’ from the Bell Pediatric cohort in the 1980’s actually scored significantly
lower on some functionality/wellness surveys than the healthy controls – suggesting that
while they were
better relative to how ill they had been but they were not ‘recovered’ or completely well. This brings to mind
Staci Stevens statement that few people ‘really recover’; while they can definitely improve what they really get good at is
managing their illness within definite boundaries…..ie. . they are still fish swimming in the ME/CFS water.
The Hanson study was more a beginning point than an endpoint, by the way. Dr. Hansen called it a ’20/20′ study which suggested to me
that they just had a quick snapshot of something they will be digging into more deeply. Dr. Hansen stated “
We are still working out our assays for looking for the MLV-like viruses. We have a number of assays that we have tried, and I’m going to mention these. But we’re still not sure which are the best ones to use. We have results
from all the different assays, but we are still, as I said, in progress..
She is being very careful about contamination; collecting blood in a special
room, UV irradiating all tubes before using them, and UV irradiating the first PCR stage. They sequence everything
they find to ensure that they are getting the sequences they are looking for. (The WPI does the same thing).
Fully twenty percent of her 20 controls were positive – a surprisingly high number – which she attributed to
them living near, and sometimes being the friends of, some of the people with ME/CFS.
Cranky PCR’s – the most shocking thing about her presentation came when she talked about
getting different results on different machines and the ‘limits’ of detection. We are at the limits of detection. We will have a sample positive one time and then negative another and then positive the third time. The PCR is really tricky. As I said, sometimes when we got inconsistent results, we discovered that one person was using one PCR machine and another person was using the other. So you really are at the limits of detection with the PCR. That’s why
we want to get at least two positive results before we count a sample as positive.
LnCap and XMRV AND MLV’s? – in her presentation in Sweden Dr. Mikovits suggested whether the LnCap cells researchers are
using to culture XMRV just weren’t very effective at growing MLV’s. This is what Dr. Klimas had heard but Dr. Hanson had
a different experience, stating…That is the conventional wisdom. We have actually never seen what is called classic XMRV. We have only gotten these polytropic-like sequences from the LNCaP cells. I can’t explain that at this point,
but, in fact, what we are seeing is polytropic-like virus in the LNCaP cells.
We’ve kind of forgotten about positive Hanson study after the excitement from the Lo/Alter study but it seems likely that more surprises may very well be in store from her. Dr. Hanson is still the
only researcher other than Dr. Lipkin to have scored an NIH grant on CFS and XMRV.
The Bagni Connection –
Dr. Bagni is definitely getting around…In her presentation in Sweden Dr. Mikovits noted that Dr. Bagni correctly identified a
high percentage of WPI positives using her antibody test and here, Dr. Hanson reported she did much the same thing with her
samples. (This means the Bagni is not ‘specific’ for XMRV but picks up MLV’s as well.) Dr.
Bagni co-authored the original Science paper and has published 7 papers over the
past five years or so – mostly on Karposi’s sarcoma. She seems to be in the
thick of things regarding antibodies which suggests that we’ll hear more from
Dr. Lo’s Unique mtDNA test – we get the idea that an mtDNA or IAP test is something
you pick up off the shelf….but many of these tests are being developed as we go along. A closer look at the
Dr. Lo’s testimony indicated that he had developed an entirely new mtDNA assay…and then used it to
check his other assays….This is the assay that is 1,000 times more sensitive than the PCR assay they
are using to check for XMRV…and its the one Dr. Hanson wants to get her hands on.
Can this be a contamination by mouse DNA? The mouse DNA genome contains endogenously
many copies of the related retrovirus sequences. We thought this would be necessary for us to
develop an assay to verify that there is no contamination of mouse DNA in the assay system we use and
also in the clinical samples that test positive for MLV-like virus gene sequences.
Dr. Coffin’s Learning Curve – After that it was kind of shocking to read Dr. Coffin say that
he actually recommended Dr. Lo do the mtDNA assay….before he recommended that he not do it. When
experts like Coffin get befuddled like this we are surely on the cutting edge of science. Of course, like
Dr. Coffin has developed his own assay – an IAP assay which he stated was more sensitive -and
which suggested to him that what appeared to be MLV’s were, in fact, contamination.
Dr. Klimas and Sample Storage – Dr. Klimas, who is not a retrovirologist, jumped in with a question about
sample storage, of all things. Dr. Klimas asked about freezing and rethawing the original samples –
something Dr. Mikovits later suggested in her Swedish talk could disrupt the virus –
making it impossible to find. She stated that only the WPI and Dr. Lo had used samples had
not been refrozen several times. Dr. Peterson, who has completely dropped out of sight on XMRV, but is
rarely in sight anyway :), early on noted they had dug XMRV out of a 20- something year
old sample but even that sample might fit the bill if it had remained frozen throughout.
DR. KLIMAS: The samples that were in the freezer all these many years, had they been manipulated — frozen/thawed or in any way —
DR. LO: No. Regional samples in this study have been kept frozen for all this period of time. They have
never been thawed out to use for different studies.
- Canada XMRV/Viral Studies Reportedly Under Way – In the’Hope for ME/CFS Sufferers’ blog Dr. Timothy Luckett states two viral studies are underway at the
University of Alberta in Canada. Here is what was posted “Dr. Mason’s study is about trialling antiretrovirals, finding causation, transmission, and prevalence. The study by Tyrell and Houghton is to show cause.
In a recent talk, Dr. Tyrell states that “I have suspected that CFS is a communicable viral disease since the Incline Village Outbreak at the beginning of my career, and I am confident that we are closing in fast,
and excluding viral pathogenesis at this point would be utter foolishness.”. Dr. Houghton is a CFSAC
panel member who has expresssed interest in herpesviruses role in ME/CFS.
- Happy New Year to the WPI – CrafterKate (VillageLife on the PR Forums) has
created another beautiful poster to say Happy New Year to the WPI
- Another ‘XMRV Conference’
– XMRV won’t be headlining the HTLV and Related Viruses Retrovirology
Conference in Belgium from June 5th to 8th but it will be one of the three main topics. The Scientific
Committe for the XMRV session includes Dr. Silverman of the Cleveland Clinic (original co-author) and Dr.
Heineine of the CDC. Thanks to Overstressed for finding this.
- ‘Intrepid’ Researcher Starts New XMRV Study – Dr. Joliceur was unable to find XMRV
in his first go around but he is having another look. In this study – which is
similar to the Dusty Miller study that we believe will get started soon – Dr.
Joliceur will be looking for XMRV in people who already tested positive
for the virus. Good luck to another researcher willing to brave the sometime
“From ME/FM Action Network – Dr. Paul Jolicoeur is a researcher in Montreal who is doing research on the virus XMRV.
He is looking for patients to act as positive blood controls for his study on XMRV. He is requesting that due to distance difficulties only patients in Ontario diagnosed with ME/CFS who have previously tested positive for XMRV on the blood test by the Reno Nevada testing centre contact him at his address. He needs blood samples of positive patients to act as positive controls in his research study about the SMRV virus. He wants you to contact him directly at:Paul Jolicoeur M.D. PhD.
Clinical Research Institute of Montreal
110 W Pine Aven
Canada H2W 1R7
E-Mail: email@example.com ”
- Whittemore-Peterson-Institute Says Happy New Year – Nothing Has Changed
– Annette Whittemore
started the year out with something of a blast – taking the Welcome Trust author to task for his statements that
XMRV does not cause CFS…and that the results of their study remain fully valid
and are backed up by multiple layers of evidence – in contrast to the PCR studies…and noted that
100’s of individuals diagnosed with ME/CFS have tested positive for XMRV. She stated that
the only thing the Retrovirology
papers indicated was that XMRV studies cannot be undertaken in a mouse lab without
extreme caution (the WPI is not a mouse lab) and should not rely solely on PCR.
She suggested that one reason for XMRV’s difficulties was that it
threatened scientific dogma….and that overturning scientific dogma required
unusually high levels of evidence and then provided glimpse of the WPI’s vision of XMRV – or rather the family of gamma retroviruses – and it is a big one;
that they believe these infections underly neuro-immune diseases and untold numbers of cancer.
She made it clear that the WPI believes that it’s past time for novel treatment trials. She also noted that the WPI’s research projects are revealing that an array of neuro-immune disorders
are infectious and inflammatory in nature. She noted that
XMRV researchers are ‘enthusiastically’ continuing to deepen their understanding of the pathogen.
For more on
- Dr. Mikovits Talks in Sweden
– A relaxed looking Dr. Mikovits gave an engrossing lecture in Sweden that provided some
new findings on XMRV…a quicker test…independent antibody validation of the WPI’s results….a different
and undisclosed storage problem…..Check it out in this overview of her talk.
(Thanks to Ann for the link).
- Dusty Miller Study Saga Continues – Ecoclimber posted a
prospective XMRV pilot study from Dusty Miller, a noted retrovirologist at
the Fred Hutchinson Cancer Institute on the both the Phoenix Rising and ME/CFS
Forums to begin to round up people who had tested positive for XMRV. The posting
was meant to be followed up with a fuller explanation of the study and an
interview with Dusty Miller explaining the study and his research but the
posting turned out to be premature as IRB approval had not been granted. The
post was quickly removed from the PR Forums but unfortunately stayed up on the
ME/CFS Forums where it received a reception not unlike a CBT trial might
Soon posts and blogs went up warning ME/CFS patients not to take part
in the study..Both Dusty Miller and an assistant showed up at various times to
try to answer questions. Miller was accused of not having any experience in
MLV’s (some fact-checking was definitely missed on that one:)) and Andy, his
assistant – was accused of lying Many members, of course, understandably simply
wanted more information on what could be a very important study on XMRV…..
Finally it was confirmed that Dusty Miller was Dusty Miller and that Andy was
Andy…and a set of questions has been deposited with him that will hopefully
clear up some fears.
The fate of the study to my knowledge is unclear. It still
needs to receive IRB approval; if and when that happens and the study resumes
the scope and methods of the study will be fully revealed and then the
discussion will begin anew
Check out an evenhanded blog on the happenings.
Exhausted by Illness and Doubts – the NYTimes plopped a largely sympathetic
and even-handed article on XMRV and CFS into its popular Tues Health section.
Highlighting what a volatile issue XMRV has been over the past year, the article
documented the ups and downs of the past year; the FDA panel recommending that
blood donations be banned, the four Retrovirology papers that shortly followed,
the emphatic statements by Greg Tower that it was over, Dr. Racaniello’s
agreement, then his backtrack then his outright rebuttal and Dr. Mikovits
refutation. Mary Schweitzer got in there and Michael Allen got the last word in
saying essentially ‘walk in my shoes for awhile and then tell me not to try
The Blog! – Even better, truly are the comments underneath a NYT’s blog pointing to the article. The NYT
probably guessed they would get a boatful of comments and they did – with 112
comments already – helped out in part by a “Dr. Santana” who
said all people with ME/CFS need to do is, yes, exercise more…..to get better…
and ‘Skeptic’ clearly hailing from the UK, who believes we will all being see
psychs in the future…..
- Viral Integration into the Human Gene….1/2 Way There –
Dr. Racaniello gave us a
science lesson on viral integration in his Virology Blog. We keep hearing that viral integration into the human
genome will go a long way to lay to rest some researchers fears about XMRV. It
turns out that viral integration is just like it sounds. Once a virus gets into a cell it uses an enzyme called reverse transcriptase to
turn its single-stranded RNA genome into the double-stranded DNA used by our cells. Then it uses an
enzyme called integrase to integrate the viral DNA into our DNA. How to confirm this has happened? ‘Simply’
amplify the viral DNA sequences and determine if they are bordered by human DNA.
(‘Simply’ may considerably understate the complexity of this task since it has
not occurred with ME/CFS yet and only partially prostate cancer). If viral DNA
is bordered by human DNA you have evidence that the virus has entered a human
cell and burrowed into human DNA. At that point it doesn’t matter where the virus came
from; it’s now infected a human cell and is now an infectious human virus.
Why is XMRV only halfway there? Because the Silverman team proved that one side of the
virus was bordered by human DNA but not the other. Although they were able to show
human DNA was present in every sample, and if one side is integrated in human
DNA, it would seem strange that the other side wouldn’t be, Dr. Raccaniello wants more.
The isolation of the entire proviral DNA, including both flanking integration sites, from patients with prostate cancer or chronic fatigue syndrome
would be additional evidence that XMRV is a virus that infects humans.
Finding XMRV was integrated into human DNA would still apparently not clinch
Dr. Racaniello – note that he’ll only go so far as to say ‘it would be additional evidence’…One wonders what
would clinch XMRV being a human infectious virus for him (and I will ask in his blog).
Down the Rabbithole – Dr. Alan Dove, in a comment posted to the blog, wants to dot even more i’s and cross
some more t’s. He stated that
Besides looking at the other end to check for duplication, I’d also want to see some blinded samples from healthy controls. That’s especially important in this case, as they’re doing a preliminary linear amplification on the patient samples before doing the junction PCR. With that much amplification,
and with the first step open-ended, I think there’s some room for PCR artifacts.
- The ‘Hard Truth’ from Dr. Deckoff-Jones
– she’s never been a
cheerleader but has always presented her and her daughters story in a very sober
manner – a very difficult thing to do when you’re representing the hopes of many
people. Her latest post starts off “
- Dr. Rein and Dr. Racaniello on Twiv cont.- Dr. Rein emphasized an important point on sequence variation. He noted that if the sequence you’re looking for is a little different from the published sequence then you can miss it. He said that was an inherent ‘risk’ in PCR and can lead to false negatives. (That risk does not apply to the immunohistochemistry results – which are just coming on CFS now). From that we can conclude that sequence variation is a real question given the newness of XMRV and how little researchers understand it. How antibodies constructed to match up XMRV and other similar viruses should be able to pick it up.
The Big “C” again (and again).
They went into a scary scenario – which does not seem to playing out at all – of the water controls researchers use possibly being contaminated from mouse DNA from mouse droppings coming from reservoirs. (No water controls have tested positive….this is not an issue with the XMRV studies). They
then went on for a while about contamination possibilities…a millionth of a microliter of mouse DNA (much less than a cell) would be detectable da da
da….no need to spell out all the gory details.
The 22Rv1 cell line – Not a Smoking Gun – The 22RV1 cell line has become an area of controversy. Dr. Rein reported that he found that the cell line produces XMRV; ie has become infected with XMRV probably when it was passed through nude mice a couple of decades ago. One of the papers found that XMRV was less diverse than the XMRV in the cell line and therefore concluded that XMRV was probably derived from it. This may have been THE major finding of the four papers – and it seemed very convincing at first but doubts have definitely crept in….Dr. Rein did not agree it was possible to conclude that XMRV was derived from that cell line, and after being initially rocked by the finding, Dr. Racaniello came to the same conclusion. In fact 3 of the 4 commentators – after cheerily espousing on all the dangers of contamination – all agreed that this central finding had been overstated and one of them actually put up a blog post about that. The papers do put a stronger focus on the possibilities of contamination – and the 22RV1 theory could be correct but it has certainly not been proven to be correct or to apply to the WPI’s or other studies. They all agreed that what the field needs is what it is doing; creating strict protocols and sharing samples between labs.
A Definitive Test – XMRV Integration into human DNA. What clinched XMRV for prostate cancer was showing that it was integrated into human DNA. Dr. Rein wanted that finding replicated by other labs and it to be extended to CFS. He noted that Illa Singh is trying very hard to do that; the problem is that it takes a lot of DNA and prostate tumor biopsies do not provide much of that….
What about those Antibodies? They finally got to the big question the patients have been asking – what about those antibodies? Doesn’t
THAT prove a real infection has occurred? Dr. Rein simply said… another lab
needs to replicate those findings. (Dr. Mikovits has reported that Dr. Bagni’s
antibody test at the NCI confirms the WPI’s findings; her study has not been
published yet.) Of course many labs are developing their own antibody tests and
some are finding it and some are not…..
Doesn’t the ability to transfer virus from blood to cells in culture mean virus is there?
– This has been a big argument from the WPI. Dr. Rein stated that if XMRV is floating around in the lab then it could get into the
samples that way.
How could ME/CFS samples consistently show higher rates of XMRV infection than the controls? Dr. Rein suggested if the ME/CFS samples were handled more
it might….but otherwise he didn’t have an answer to that and said he didn’t think ‘we’ have an answer to that.
What is next? Using validated assays…exchanging samples…..using different labs. Dr. Rein does not believe that large-scale case-control human studies are called for – which makes sense; what assay, after all
,are you going to use to test all those people? Instead he called for developing a consensus assay and then moving on – which is essentially what is occurring.
He was clear that he believes it’s possible that XMRV was a ‘mistake’ (I think
he leans this way given the way his prostate studies have turned out) or that it
is is a virus infecting people.
Conclusion – discussing the four Retrovirology papers was
never destined to be a fun experience. However, all the researchers agreed the
XMRV’s options are still very much open and that we still have much more to
learn and that several of the ongoing should tell us a lot.
Dr. Alan Dove – one of the participants in the Twiv talks takes researchers
on both sides of the XMRV to task for going too far in his blog.
- Retrovirology Study Media Roundup – A check on Google news came
up with no less than 135 articles on the Retrovirology papers, most of which
overhyped the findings – helped to a great extent, no doubt, by co-author Greg
Towers rather definitive statements. The top story, though, was by Nature.com
which came to a more sedate conclusion typified by Dr. Lipkin’s remarks
- Next Up – an interesting seminar from Dr. Mikovits in Sweden
(thanks to Ann!).
- Blood Working Group Reacts – everybody seems to feel the need to react to the four papers on
contamination in the Retrovirology Journal of all about a week ago. The BWG stated, yes,
of course, we and the labs are and always have been concerned about contamination and they are proceeding with phase III
which will look for RNA, DNA and antibodies. Interestingly, they talk about culturing this is something that we thought
that the BWG, which is focused on faster methods of detection, was not going to do
but they noted how important it is to be able to
culture (and isolate?) the virus itself and antibodies to it. As Dr. Lipkin noted in his comment PCR is
not the end-all and be-all of testing for viruses and the BWG appears to agree.
This Week in Virology – session #112 of the Twiv podcast with Dr.
Racaniello featured XMRV and the head ofthe National Cancer Institute, Dr. Alan
Rein. They started off tonight with a good laugh when Dr. Racaniello told Dr.
Rein they had a him on so he could clear up all the issues regarding XMRV. Dr.
Rein has worked extensively on murine leukemia viruses and HIV. Dr. Rein noted
that the gene sequences found by Dr. Lo and Alter were gene sequences commonly
found in mouse DNA and in endogenous retroviruses. Dr R noted that they went to
a lot of trouble to ensure that these are not gene sequences from mice. Dr. Rein
agreed that did not think that the mitochondrial DNA test that they did was the
best test for mouse DNA and felt that IAP DNA assay would have been quite a bit
Because one study showed it was possible for a mtDNA test to miss mouse DNA
that the IAP test is able to pick up they agreed that it would be best for the positive
studies to go back and retest their samples using the IAP test. (This suggests, though, that the
mtDNA is completely inadequate for finding mouse DNA. Sure it’s possible that it misread some
samples…but how is it possible for it to misread 70 out of 100 samples? So, yes, for accuracies
sake, go back and retest the samples….but to fine tune the results – not overturn them…
Variable enough? -a big question making the rounds is if XMRV (or the Lo/Alter sequences)
are genetically variable enough. A replicating virus should be quite variable from person to person while a contaminant
would not. XMRV does
not, as yet appear to be very variable genetically. Dr. Rein noted, however, that XMRV is very different from HIV and, given
that, there is really no way to tell how variable a replicating XMRV should be.
The Prostate and Dr. Singh – Dr. Rein also looked for XMRV
in hundreds of prostate cells and found none. Rather disturbingly he described a
process, too complicated for me to get on the first pass, in which it was
possibly for immunohistochemistry samples to register as false positives.
Immunohistochemistry has been Dr. Singh’s bailwick; she has claimed that
immunohistochemistry is more accurate than PCR in finding XMRV but Dr. Rein reported that his analysis of
some of Dr. Singh’s positive slides suggested that they were actually negative. Dr. Singh, appears to be
using immunohistochemistry in her XMRV autopsy study. Dr. Singh, of course, was not on the program and did not have a chance to defend
her study. Dr. R did note that a recent paper came out that did found XMRV in prostate cancer tisssues…..the twists and turns this field
is still taking continue to be amazing.
More on the podcast tomorrow.
- Dr. Racaniello Retracts Statement About XMRV and CFS– showing an admirable commitment to the pursuit of the truth Dr Racaniello made an abrupt about face regarding his statement that the four papers were ‘probably the beginning of the end of XMRV and CFS’. His new blog “XMRV and CFS- It’s Not the End’ paints a very different picture and, to me, Dr Racaniello’s new piece demonstrates just how difficult a subject this is. Dr. Racaniello runs a research lab – he is well versed in this field yet this is what it took for him to alter his opinion
“I read the papers over again, and began checking XMRV sequences in Genbank. I also began an email correspondence with authors of three of the four papers, and spoke with my virology colleagues here at Columbia. As a consequence of this additional research I decided that my initial impression of the papers was incorrect, which is evident in my post entitled ‘Is XMRV a laboratory contaminant?”
This is difficult stuff! He does believe that the new papers do highlight the dangers of contamination but they do not imply that the positive results from the WPI’s or other studies were contaminated. He is fully in line with Dr. Coffin, here, who co-authored two of those papers.
“Upon re-reading three of the four Retrovirology papers it became clear to me that they show that identification of XMRV can be fraught with contamination problems, but they do not imply that previously published studies are compromised by these findings. Clearly any new studies done on XMRV should keep in mind the potential for contamination from PCR kits and murine nucleic acids.”
Three of the papers were nothing but warnings; the Hue paper was the most substantial one and the one that bothered him the most but here, again, he was able to find reasons, some of which the WPI mentioned in their rebuttal, why the Hue paper might not apply to the WPI’s findings. He seems to be indicating, oddly enough, that some XMRV isolates appear to be laboratory contaminants while others do not – was an amazing twist in an already very complex field! However, this is a twist that should be able to accounted for one would think – simply by analyzing the different strains (?). Vectors from the MoMLV virus appeared to be used in gene therapy, by the way, which is one reason they might be present in labs. The WPI, however, said the type of mice Hue described have not been used in their labs.
The idea that PCR amplification could itself cause increased variability in 22Rv1 making it look like the ancestor to XMRV indicated just how complex all this is. Willow on the Phoenix Rising Forums has provided a way this could occur.
“I was initially more troubled by the fourth paper by Hue and colleagues. There are four major findings in this paper (gag PCR primers are not specific for XMRV; the virus is present in 5 human tumor cell lines; two XMRV isolates are nearly identical to a virus from the human prostate cell line and also contain an insertion from the murine retrovirus MoMLV; and there is more nucleotide diversity in viral sequences from 22Rv1 cells than in all the patient XMRV sequences). The fact that two XMRV isolates seem to be laboratory contaminants – judged by the presence of MoMLV sequences – was initially unsettling until it became clear that other XMRV isolates do not have this insertion. That leaves the fourth finding – that XMRV from 22Rv1 cells appears ancestral to, and more diverse than, all the human XMRV sequences. I decided that this result was less troublesome than I had originally believed, in part because it is not clear that the differences among the 22Rv1 viruses did not arise during PCR amplification.”
He concluded the blog with an apology and stated that the research on XMRV and CFS must proceed and, in fact, called for it to increase.
My conclusion is that these four papers point out how identification of XMRV from human specimens can be complicated by contamination, but they do not mean that previous studies were compromised. They serve as an important reminder that future experiments to identify XMRV need to be appropriately controlled to ensure that the results are not compromised by contamination.
In other words, these four papers are NOT the beginning of the end of XMRV and CFS. Rather, research on the role of this virus in human disease must proceed, with large, case-controlled epidemiological studies, as suggested by others.
I would like to apologize to anyone who was offended, angered, or disappointed in any way by my statement to the Chicago Tribune. It is my goal to educate the public about virology, and clearly I did not do that very well.
There are at least two lessons that you can take away from this incident. First, that I make mistakes, and that I’m willing to admit it. Everyone does, including scientists. Second, if I had difficulties interpreting these papers, how would non-scientists fare?
The Chicago Tribune has printed his retraction
- Respected Retrovirologist Tackles XMRV/Retrovirology ‘Superteam’ Formed to Rebut Claims – the biggest news of the day, however, was not Dr. Racaniello’s retraction but EcoClimber’s statement on the Phoenix Rising Forums stating that the Retrovirology papers have prompted noted retroviriologist Dr. Dusty Miller at the Fred Hutchinson Cancer Research Institute in Seattle, Washington to dive into his lab to investigate the contamination claims – which he does not believe will pan out and will apparently be part of a XMRV retroviral ‘superteam’ that will rebut the claims in an organized fashion. By suggesting XMRV was a contamination – wherever it appeared – Hue’s paper stepped on a lot of toes. It was Silverman, after all, who discovered XMRV in March of 2006 and since then has published 12 papers on it. Klein has been a co-author of several his papers and, of course, Dr. Ruscetti – who is very well respected in the field, was a co-author of the Science paper.These researchers may very well be doing lab work to specifically counter the Hue papers findings. Ecoclimber stated
I talked to Dr. Dusty Miller. His lab is currently in the stage in testing and experimenting and gathering the evidence to rebut their claims. He states he can refute their claims. He will be getting together with Ruscetti, Silverman, Klein, Smith and others to post their rebuttal as a group against the negative papers.
- Annette Whittemore, Dr. Mikovits on Nevada Newsmakers meanwhile Dr. Mikovits and Annette Whittemore appeared on Nevada Newsmakers to counter the claims of contamination that have been raised by a rather lazy media. Annette painted ME/CFS in broad terms – it is a complex illness that the WPI believes is infectious, involves many pathogens and affects the neuroimmune system and Dr. Mikovits noted the WPI has had interactions with researchers in countries around the world including Norway, Belgium and Spain. Dr Mikovits asserted that multiple tests are needed to detect XMRV because no single test (ie the PCR results in Retrovirology) is accurate enough. (Dr. Lipkin made a similar point in an email).Dr. Mikovits noted that they were ‘well aware’ of the potential for contamination to skew the results, which, of course is doubly true given co-author Dr. Sandra Ruscetti’s background in mouse retroviruses and Dr. Mikovits close connection to the Ruscetti’s. Annette Whittemore stated that the Retrovirology papers ‘do not change their findings’ and that “we are moving forward in a positive way”. She also noted that they were not apprised of the results before they were published – suggesting that the original authors are usually give a bit of lead time to respond to negative papers published regarding their findings. Dr. Mikovits noted that any large discovery is going to lead to ‘a lot of pushback’ because the best science always leads to ‘more questions than answers’ and that’s what has happened. (Has it ever! The XMRV discovery pushed researchers into fields and into digging up questions that they had never asked before.)
When the interviewer asked Dr. Mikovits why researchers have not followed the exact methods of the original paper her reply was very interesting. She said that researcher do what they know how to do well and that they do the advances of the last decade very well but that those kinds of techniques are just not ready to take on a new virus like this. (If I paraphrased correctly!)
Those new techniques have replaced the old-fashioned method of culturing, which is difficult, expensive and time consuming. (Dr. Mikovits has been saying it’s not about the
PCR for months). She said researchers think ‘if we can detect HIV using this method we should be able to detect this virus” but
‘that is just not the case at this point, it is too early in the discovery process”.
Caught in a Time Warp? (This point
has confused me because they did use PCR to detect the gag sequence in the original paper and PCR. of course, is described by
other commentators as something virtually any lab can do. How does this laymen make sense of all this? Perhaps PCR detection of XMRV is so difficult that just the right techniques required to find it.
It could be that small things, unbeknownst to the research community now, are able to knock XMRV off – and this is in fact what
the NCI is looking at. In that case, until the PCR techniques are perfected then culturing and growing more virus and then studying it –
figuring out it’s little secrets – and then developing the correct PCR test would seem to make sense. I am just a laymen – no special expertise here – trying to think through these issues. .Sometimes I get it right – sometimes I get it wrong; take everything printed here with that grain of salt!
Unfortunately the PCR test was regarded as the main finding of the Science paper – it was what got the lion’s share of attention, and PCR, as Dr Mikovits pointed out, is what researchers in this field generally do now…. Dr. Lipkin and Dr. Miller and others are wary of PCR as the be-all and end-all of detecting viruses, and they are pursuing other means…
Annette Whittemore noted all the other groups at the NIH, NCI, Cornell and University of Utah that are moving forward. When asked about politics Annette Whittemore noted that these issues are money intensive with a lot of stakeholders and some politics is inevitable….When XMRV turns out its going to cost some stakeholders a lot of money (and, of course, make money for some others).
WPI Clinic Physician Chosen A physician has been chosen and it sounds like the clinic and research sides are coming together.
and the immune signature paper on the XMRV published should be published early next year. Dr. Mikovits and Annette Whittemore were quite poised during this
rather turbulent time and acquit themselves and the organization well, IMHO.
- The Retrovirology Papers: Day Two – Not surprisingly the media jumped on the titillating but wrong story and stated XMRV was done and that it was not the cause of ME/CFS. XMRV certainly did take a hit, yesterday, but several important names, particularly Dr. Coffin – who was a co-author of two of the papers , and has been doing his own research on how to tell XMRV apart from a contaminant, refused to fold XMRV’s tent stating that the arguments against XMRV were subtle and indirect and that none of them directly indicated the WPI had inadvertently come with a contaminant.
Indeed three of the four papers demonstrated that they had found a contaminant but not that the WPI did. The Robinson paper indicated that one test for contamination that neither the WPI or the Lo lab used(?) was more sensitive than the mtDNA test that the WPI reportedly used. But it was only MORE sensitive; even if the WPI or Lo study mischaracterized some contaminated samples there was nothing in the report to suggest that they mischaracterized ALL of them – something that doesn’t appear to be even remotely tenable. Similarly, the Oakes paper described a situation where tests for contamination revealed that yes, contamination was present. It’s certainly a warning but both the WPI and the Alter studies tested for contamination and they did not find it.
The Hue paper – was the only potential body blow to XMRV of the four. Dr. Hue’s phylogenetic analysis suggested that XMRV was not derived from a wild mouse but came from a cell line grown in a laboratory. Hue’s argument was that if XMRV was a human pathogen that is widespread in the population – as studies suggest it is – then it would have, like HIV, and other viruses picked up a great deal of variability. But Hue found that XMRV was actually less variable than the 22RV1 cell line his analyses suggested it was derived from. Hue, however, only used two full length XMRV genomes for ME/CFS patients in his analysis. Whether or not he needed more is unclear – he also used 1 representative of other mouse viruses in his analysis but it does make one wonder about the many unsequenced strains sitting in the WPI’s labs. Whether including them might possibly have altered his results is a question for a population geneticist….
Hue also showed that the standard PCR test for XMRV was not as specific as had been originally thought and that it can misidentifies endogenous MLV sequences from some mouse strains as being XMRV. The misidentification is something of chimera for the WPI; the fact that they could grow viruses indicated that they did find XMRV. The WPI countered with the fact that a) they can grow the virus – so the PCR results were not simply the result of some mouse DNA getting into their samples and that their antibody test indicated an immune response had been created to a virus, not a contaminant. They did not reply to concerns about Hue’s phylogenetic analysis.
Dr. Racaniello Does a Partial Turnaround – To read that Dr. Racaniello said that XMRV’s course in CFS was probably over was rough, considering that he has been considered to be an objective source. Over night, however, Dr. Racaniello reconsidered his opinion and the next day concluded that, while his concerns remained, he had overstated “I do not believe that the four Retrovirology papers prove that XMRV is
not involved in human disease.”
- Retrovirology Journal Publishes Four Studies on XMRV and Contamination Retrovirology today published
four studies that focus on the contamination issue with XMRV. None of them are definitive, and none of them demonstrate
that contamination resulted in the findings of the original paper, but they do indicate how careful researchers have to
be when they explore this particular line of viruses..
WPI responds – the WPI quickly responded stating theirs and Dr. Lo’s samples were examined extensively for
contamination and that their ability to grow live virus and the presence of antibodies indicated that
contamination was impossible. > –
- Amy Dockser Marcus has a nice succinct blog on the meeting
- The Limits of the Blood Working Group – the CAA’s Webinar– we’ve been kind of thinking that the Blood Working Group (BWG) is a be-all and end-all study but now we can clearly see the limits of their approach. They use very rapid testing procedures to test the blood – which means that they are not at all interested in culturing the virus. The problem with that is that the data WPI provided and their own statements indicate that rapid testing procedures are just not very accurate at this point.(Indeed they don’t appear to be used either; my understanding is that the WPI uses culture tests instead of straight PCR and antibody tests now)
If you go back and look at the chart that shows the results of the testing the WPI did on those for patients you’ll see that they about often as not got conflicting results using standard PCR techniques. This is not really surprising since we’ve heard they’ve often had to retest the samples several times until they got a positive result
The culture test, on the other, provides remarkably consistent results; time after time, samples that were problematic using the PCR, were positive using the culture test. But even here XMRV is difficult. The long culture time (21-42 days) indicates that even when you give XMRV a boost; when you rub it’s belly and sing soft words in it’s ears (ie you culture it)- it still takes longer than normal to show up. (Most labs culture for 10-12 days).Still the fact that it does show up very consistently does make one wonder if a good deal of the problems here could simply be the difficulty of the research community coming to terms with one of the rarest viruses yet detected in the human blood.
Unfortunately culture tests are not used to test the blood supply and the BWG will not be assessing them.
The Original Finding Begs to Differ – Theoretically that shouldn’t be a problem; both the WPI and Cleveland Clinic were able to find that ‘gag’ sequence without culturing or doing anything fancy – simply by using nested PCR – in the CFS patients in the original paper. Its true that they reported that they had to search some of the samples several times – but they also found it right in others. That suggests that while other labs that did one round of testing might have a harder time finding it they should be able to find – in lesser numbers. This really should not be a problem. Indeed, given the talk of treatment studies in six months – it’s hard to believe that anyone at the time thought validating XMRV was going to be difficult. Yet, last Oct was the last time “XMRV” itself has shown up in a non WPI supervised or VIPDx CFS study.
Why that is happening is still a mystery.
Not Storage or Preparation! – Dr. Mikovits stated at the Workshop that the storage/preparation was a major factor in the differing results but Phase II ended with no major storage/preparation issues (and one side study exploring one factor) and a mystery why XMRV seemed to want to pop up sporadically at Day II in a couple of labs.
Possible Causes of the Disparities – Graham Simmons came up with three reasons why all the labs are not finding XMRV; subtle sequence variation/contamination/and the bug is right at the levels of detection….. Notice that we finally got the cohort question kicked off but the rest remain the same.
If XMRV turns out the XMRV story may simply be a testament to the WPI’s sheer tenacity in looking for this virus. …once they got hint of it they like a dog with a bone and they left no stone unturned to find it; they tested samples multiple times to see if it would show up and they put it in culture long after other labs would have given up…
NCI Collaboration – on a Norwegian Radio Program Dr. Mikovits reported “We’ve worked very hard with the National Cancer Institute
to standardize the assays and standardize the tests so we can use the same reagants and same tests so we can be comparing apples
to apples.” Two labs working together to test each others results and decide on the best tests definitely sounds like what’s wanted and needed. The NCI and WPI had
very different results this round; how nice it would be to see these two labs match up the same results next time.
Time, Time, Time – It was disheartening to learn that, after all this time, the BWG had only tested 5 samples, one of which was negative. Dr. Simmons pointed out they had, in fact, 10 pedigreed negative samples but only used one – perhaps because they are holding the others back for the big study. The BWG has taken enough of a beating on the time issue for Dr. Simmons to produce a chart showing what had happened.
Alex3619 on the Phoenix Rising Forums dug into the chart that was presented and noted that two of the really lengthy issues were outside of the BWG’s control; in order to ensure that the negative samples were really negative they were tested and cultured by all the labs for up to 42 days plus the ethical review board took up a good chunk of time.
Blood collection for Phase III which will involve many more samples and more laboratories will start in January and the testing will reportedly take about 6 months
If XMRV is validated in CFS and the blood supply expect a lot of action with studies already being planned to search 2,000 blood samples dating backing to the 1970’s to see when it showed and what it might have caused.
- A Wild Day- the Blood Working Group Reports – All thanks have to go to ValB626 on the MECFS Forums for just pouring out page after page of details from the hours of testimony and discussion on XMRV. Without it we would have had very little.It was exciting, we learned quite a bit but unfortunately little resolution was in sight and in some ways the two sides seem to have dug in deeper. It seems clear, for instance, that Dr. Stoye has made up his mind. Dr. Coffin seems to be more concerned about the possibility of contamination than before and probed Alter/Lo quite strongly but is waiting for more evidence before he makes up his mind.
On the other hand Dr. Lo and Alter seemed very confident in their findings and asserted they have done the most sensitive tests for contamination. (Dr. Hansen later reported that she was considering switching to the Lo/Alter mtDNA test). Dr. Lo ended with a strong defense of his findings (and a little swipe at the ‘anecdotal’ evidence presented by Stoye) and with what appeared to be an empassioned appeal for more research into CFS. (He seems to be yet another figure who probably wouldn’t have come near CFS with a 10-foot pole before XMRV but has gotten hooked just as Ruscetti did, and Houghton on the CFSAC panel (another Lasker winner) and now Dr. Lipkin, it appears.
The Test that Binds – What Coffin and others would really like to see from Drs. Lo/Alter is a live virus and/or evidence of p MLV integration into human DNA. Interestingly, the way it was worded on Vals posts Coffin didn’t seem to expect that this would have happened yet (No virus to go with those sequences, as yet?). The WPI’s ability to isolate the virus was a key factor in convincing the research world XMRV was real and its apparently not an easy task.
Coffin has been working on determining just what is XMRV and what is not and has developed a test that can distinguish XMRV sequences from mouse sequences. We got something of an idea where he was coming from when he stated that two papers (authored by Dr. Huber and Dr. McClure?) will soon appear that determine what looked like XMRV in CFS patients was actually mouse DNA. (There was also a presentation at the Workshop that was not published which related how one researcher thought she found XMRV but later determined it was contamination . The kicker there is that my understanding is that she used mtDNA to check for contamination, which, of course, Alter and Lo and the WPI did….so it doesn’t appear that that study would bear on their findings.)
Mt DNA Not Enough Coffin does not think mtDNA is
sensitive enough but Lo disagreed and, in fact said their test was more sensitive than
Coffin’s. (Love the black/whiteness of this field – the sheer clarity of it – it’s so inspiring…)
Lo also said that mouse DNA would break up when they amplify it and they had clean, clear sequences.
Lo then said even when they subcloned the sequences – they were exactly the same. Coffin then went into all the possible sources of contamination. Lo agreed but stated they put in many negatives which appears to mean they prepared many samples that were negative and then tested them……suggesting that if some mouse DNA had been floating around it could not have come from their lab.
Alter Jumps In – Then Alter apparently jumped in from the audience and provided a very strong point when he noted that they tested the old samples and did new draws and found the same gene sequences which leads to the question how do you get the same contaminant twice 15 years apart? What are the chances of that? They are using different reagants, different sampling techniques, maybe different tubes, they are processing the sample immediately – yet the same contaminant shows up…..That would be incredible….
The Limits of Detection – Hansen’s presentation emphasized how difficult this pathogen is to find.
She did check for mtDNA contamination, had blinded samples and tried several
different assays. She found pMLV, just as Alter/Lo did. (Stoye and Coffin
emphasized that pMLV’s are quite different from XMRV. (A retrovirologist I talked to
agreed; the sequences Alter/Lo found are much closer to endogenous retroviruses than XMRV is;
he would have expected the opposite; that the Alter/Lo ‘sequences’ would have clustered around it.)
Still no XMRV – XMRV has a really distinctive region that she searched for but could not find.
She did report that she thought the negative studies were caused by using the wrong primers and that they are missing the pMLV’s as well because they are searching too narrowly.
The most astonishing part of her presentation was when she
reported that two different PCR machines in the same lab tested differently; one could find it and the other could not.
She also had to do multiple ‘transfers’ (rounds?) of PCR to pick it up.
We will hear about the ‘limits of detection’ several times during the talk. Could it’s rarity in PBMC’s be what is stimying the efforts? Possibly so…
Some Recovery is Possible Without Antiretrovirals – Interestingly she found the same prevalence of XMRV in ‘severe’ CFS (POTS, etc.) and ‘recovered’ (still symptomatic but can get around) which indicates anti-retrovirals are not necessary for some recovery in some people. (Dr. Mikovits had noted this before). Coffin again pressed her about finding a complete virus…One gets the feeling that if someone could do that he would relax considerably.
Dr. Mikovits UK study – the UK study is quite impressive and it’s a shame she can’t get it published. They shipped samples to the National Cancer Institute, which, of course, has – impeccable credentials and they used a lab there that had never tested for XMRV. They also used two independent labs and everything was blinded. They cultured the samples for from three to six weeks, far longer than other studies have tried….. It was a great cohort, all Canadian Criteria, 50% homebound…if XMRV was going to show up in any patients it was going to show up in these – and it did – 78% were positive for XMRV and 4% of controls (as in the first study).
Coffin, interestingly, seemed to back off a bit. After suggesting some problem with the DERSE procedure Ruscetti jumped in from the audience to note the consistent results from both the gag and env regions.
Conclusions –A Draw! Both ‘sides’ drew a little blood and both will come back to fight another day.
Stoye is stewing about XMRV and believes the pMLV’s are just mouse DNA, Coffin is quite concerned, Drs. Lo and Alter are cooly confident, Ruscetti still can’t believe
we’re still at the diagnostic stage, Mikovits popped in with an excellent study, Hanson can find it one PCR and not another.
Hansen and Lo still can’t
find XMRV, Dr. Mikovits is finding it in spades, Hansen says the negative studies using the wrong primers, Mikovits says culture for a
few more weeks, fellas and Stoyes just scowls..the only we were missing was Dr. McClure (:) who we will apparently hear from soon)…..
Alter/Lo still need to isolate the virus or prove its embedded in human
DNA. The BWG seems to have no handle on what lab is ‘right’ and has alot more
work to do. Right now best thing to do with the BWG timelines seems to be to double them and then double them again….
We should know more after the CAA’s webinar
tomorrow at 1p EST..Hopefully we’ll get another timeline (joy), some translation of the BWG’s findings and a reason why
after all these months they only passed around four samples…
Isn’t it time for Singh autopsy study?
- Phase II of BWG Study is Complete (Really!) – The CFIDS Association today announced that the oh so
important (and time consuming) second section of the BWG’s study focusing on sample preparation
and sample storage is complete and that the results will be announced at the BWG’s meeting, just 3 days from now
(Dec 14th) (gulp). The meeting is open to the public (if you happen to be in Gaithersburg, MD) but is not webcast;
just three days later, though, a CFIDS Association webinar (register here) will feature two members of
the BWG who will talk about the results and where they go from here.
Dr LeGrice reported they were looking at contamination issues although that has never been explicitly stated.
Still, if contamination was to occur it would presumably occur during the sample preparation phase. At the very least the
Group should be able to tell us how to prepare and store an XMRV sample such that it does not disappear. This suggests they should be able to
indirectly tell us if any studies inadvertently destroyed XMRV during the sample preparation/storage phase.
Discuss the meeting here
Meeting Agenda – XMRV and the MLV’s will be the second topic on the meeting agenda. That discussion will take place from 1-3:30 pm EST. There will be nine presentations; Dr. Mikovits will make one of them. Here they are:
A. Introduction and Background, Indira Hewlett, Ph.D., DETTD, OBRR, FDA (10’)
B. Summary of Current Research on MLV-related Human Retroviruses and Disease Association, Jonathan Stoye, Ph.D., NIMR, UK ( 25’)
C. Recent Studies of Epidemiology of MLV-related Human Retroviruses:
i. U.S. Study, Shyh-Ching Lo, M.D., OCTGT, FDA (15’)
ii. U.S. Study. Maureen Hanson, Ph.D., Cornell University (15’)
iii. UK Study, Judy Mikovits, Ph.D. Whitmore Peterson Institute (15’)
D. Animal Studies: Potential Transfusion Transmission of MLV-related Human Retroviruses, Francois Villinger, Emory University (20’)
E. Update of Blood XMRV Working Group Activities, Graham Simmons, Ph.D., BSRI (15’)
F. Prospective and Retrospective U.S. Donor Surveillance Studies, Michael Busch, M.D., Ph.D., Blood Systems Research Institute (15’)
G. Assay Development Efforts on MLV-related Human Retroviruses, Rachel Bagni, Ph.D., National Cancer Institute (20’)
- XMRV in Spain: Part II – details on the Spanish study have shown up and our surmises were correct; XMRV has been found in CFS, HIV and healthy controls in Spain. The sample size was very small – so any prevalence figures are very preliminary. This is not a ‘study’ so to speak; it was an attempt – after all the controversy – to see if they can find the virus. They were able to do that and it appears they will now start testing more people. We should keep in mind that they were looking for XMRV in an somewhat different set of cells- the B Lymphocytes – than everyone else has been looking in (PBMC’s). PBMC’s contain B Lymphocytes but no one has actually signaled out this group of cells and tested it.It’s difficult to ascertain prevalence even in this small study because they reported the incidence of XMRV in cell lines rather than patients and some patients (n=11) obviously contributed more than one cell line (n=21). XMRV showed up in 3 x’s as many patients as controls using the env protein, in equal numbers of controls, CFS and HIV using the gag and twice as many CFS patients (50%) as HIV and healthy controls using the pol protein. The researchers noted the difficulty in determining prevalence -and that that was not their aim – but thought prevalence in CFS might end up, based on these early results, similar to the WPI – approximately 67%.
What we have here is a mishmash that indicates how uncertain the science is. Ideally we would want everyone who tested positive for one XMRV protein to test positive for another one. In fact, ultimately, that is how the testing will work – one positive test never denotes a positive; it has to be confirmed by another test. That is clearly not happening yet and a major goal, of course, will be to tighten up the tests so that consistent results are found across all of them.
They do suggest that B-lymphocytes could be a reservoir for XMRV; ie a place where XMRV is replicating more (or rather is actually replicating) and, in which, it is easier to find- which would be a really significant finding; however, the initial report stated the XMRV was found in very low amounts.
The most important to take away from this effort, though, is that the Spanish researchers have been able to find XMRV and they have found it in B Lymphocytes – an intriguing cell with the success of a small Rituximab trial and the herpesvirus infections found in some people with ME/CFS.
XMRV in Lymphoid Tissue in Macaques – They also showed XMRV can grow in the lymphoid tissue of Macaques . Lymph tissue is an area Dr. Mikovits has speculated could emerge as a reservoir ie a site of increased XMRV replication. That isn’t clear yet but the Spanish team did report that was no evidence that XMRV’s presence there was resulting in the deaths of immune cells -or altering immune functioning. Viruses often replicate furiously inside a cell, kill it and then swarm to the next one…Or the immune system recognizes an infected cell and responds to it. Neither of these scenario’s showed up in this early look at lymph tissues of macaques.
FunctionalityThe researchers did note, though, that XMRV could be interfering with cell functionality which actually fits in very well with ME/CFS. Immune cell numbers and composition do not appear to be radically affected in CFS – The Klimas/Fletcher studies, on the other hand, suggest that, cell functionality is quite impaired in NK cells and possibly T-cells which could be explained, on e would think, by a kind of smoldering infection characterized by low rates of replication. (Nothing seems to come easy in CFS….plummeting cell numbers aka AIDS would have quickly convinced researchers of the immune dysfunction in the disorder – and quite a few studies have been done – and they have never really shown up…Instead, impaired cell functionality has shown up – a much more difficult and subtle factor to spot.)
- Huber and McClure Studies On Their Way – It almost seems like every upturn for XMRV is immediately followed by a downturn. Both Dr. Huber’s and Dr. McClure study – both of which are focusing on contamination – will reportedly be published in the near future.
- A Still Missing Piece – the Alter/Lo Work – The sequencing work Dr’s Alter/Lo are doing will be very important
given how critical their study was for XMRV. Further sequencing will nail down, presumably for good, where the genetic sequences they found came from. Dr. LeGrice reported that the sequencing would be ‘easy’ but he didn’t state how long it will take.
Completely sequencing the virus was an important part of the WPI’s study. Shortly, hopefully we will get a definitive report
on where the sequences they found came from; mouse or man?
- The Buzz From Spain – Cristina Montane relayed a report from Dr. Julia Blanco on the meeting. Dr. Blanco
first noted the usual on XMRV: that the problematic methodologies being used impair detection, contamination could be possible for some results, the polytropic MLV findings and the need to assess anti-retroviral effectiveness.
(editorial) With regards to contamination effecting some findings ….with roughly the same percentage of positives
in people with CFS and healthy controls showing up in Dr. Cheney’s patients and the London study and the reduced levels of positives
in theVIP Dx results – it seems hard to believe that this statement applies to the WPI/VIP Dx findings. On the other hand it’s hard to
understand how a small Research lab in Reno Nevada would be able to stump much bigger and presumably more sophisticated labs
and there have been a bunch – from BSRI to the Koch Institute to the CDC’s HIV Labs…. XMRV remains a conundrum.
The NCI’s request that researchers give details that usually don’t make it into their methods section suggests they believe the problem
is more than not following the WPI’s techniques….We await Dr. Singh’s results in particular given the care she had given it…
using a PCR technique that seems almost immune to contamination…with the same blood storage and sampling techniques used for
both healthy controls…and its overlapping checks…and, of course her experience with these pathogens.
Finding XMRV! After a rather strange sounding statement which seemed to indicate that they were now stating their
results: “Considering the evaluation of our data set in the context of the knowledge we have of other retrovirus, we can point out” they then noted that
” XMRV sequences can be found in patients with CFS but also in healthy donors or HIV+ patients. The copy numbers appear to be
very low, and their pathogenic potential is unknown” which suggests, since no one to my knowledge has found XMRV in people with
HIV, that they have looked at three groups; CFS, HIV positive and healthy controls and found XMRV in each of them – a big step
forward. Simply finding XMRV is quite an accomplishment given all the zero/zero studies.
What we don’t know, of course, is what the prevalence was – an important issue! If its high in people with ME/CFS and low in health controls then we’ll another strong result. In any case they are finding XMRV and one wonders if the reason they are finding it has anything to do with Dr. Mikovits earlier trip to Spain reportedly coach a lab there on how to find the virus.
Very Rare – they also report that when they found XMRV they found it in low numbers, which, in a way is encouraging as well, since that is what we would expect.
Immune Findings Dr. Blanco reported the Spanish researchers also found alterations in B, NK and T cells. Since NK cell dysfunction is basically expected in ME/CFS, the focus here might be on those B
and T cells. Any unusual T-cell finding would be a significant development given the key, key role they play in the immune response.
A B cell finding would be very interesting as well given that a small Norway study has found that Rituximab – a B-cell depleting
monoclonal antibody – has been quite effective in some people with CFS. A paper on that with an interview with the study director, Dr. Olaf, will appear shortly on Phoenix Rising.
- Dr. Judy Mikovits Speaks – on XMRV, ME/CFS, MS, Lyme Disease, Cancer…….(is that all???). – The WPI has kind of been playing it safe it seems…but no longer…
Dr. Mikovits is going to broaden the discussion on XMRV just a little bit in Santa Rosa, Ca on Jan 17th when she talks on it’s relationship to MS, Lyme disease
and presumably other types of
cancer than prostate cancer….Early on we heard about XMRV’s possible relationship to autism and atypical MS- which was later described
as something of mistake…If the report is correct Dr. Mikovits is going to open that discussion again. One wonders if a new
paper is in the works (except we hear that Journals will not accept XMRV papers from the WPI until their findings have been completely
The study of note with regard to ‘other diseases’ is, of course, the Singh autopsy study….which should tell us just where XMRV
is found in the general population and should shed some light on its pathogenicity. If XMRV shows up in the brains of people with encephalopathy
or in the breast tissues of people who died of breast cancer…..then it’s hard to imagine the wheels won’t really come off on XMRV research
…This interesting meeting will take place from 2-5 pm
The Friedman Event Center
4676 Mayette Avenue
Santa Rosa, CA 95405
707.360.3021 for directions only
Directions and a map: http://www.friedmaneventcenter.com/location.htm
For more information please contact:
- News From Spain On XMRV and CFS – Tomorrow! – Clara Valverde on behalf of the Spanish CFS League posted an announcement stating that Spanish researchers will
announce their XMRV results tomorrow. When we last heard from Spain, Dr Montoya – an infectious disease specialist in Stanford, who has been involved in several ME/CFS studies and is currently collaborating with Dr. Lipkin on a pathology study, was in town to talk with Spanish retrovirologists. At that time the XMRV study was still underway but it appears they have some concrete news to announce.
Big Immune Finding – perhaps almost as importantly they will announce the finding of an immune deficiency in cytotoxic T-cells (CD 8) in CFS. This could be big news. Right now there is abundant evidence of problems with NK cells in CFS but NK cells, which Dr. Klimas described as a primitive form of a CD 8 cell, simply don’t get the respect that cytotoxic T-cells do. Finding an abnormality in one of the recognized heavy hitters of the immune system would be a huge win if it was validated. Dr. Klimas has stated that she’s found reduced perforin levels in cytotoxic T-cells and she’s reportedly been working to validate cytotoxic -C problems in CFS but this would be the first official announcement by a researcher. If validated it might very well turn many immunologists heads – causing many to take new look at ME/CFS.
The researchers will also suggest ways to cope with this newly discovered immune deficiency as treatments are being developed. Spain will definitely be in the ME/CFS spotlight tomorrow!
- Of Mice Men and MLV-s – With no less than four XMLV publications under her belt during the last 14 months Kozak
is the premier XMRV evolutionary biologist. Her latest paper is a review of her and others work on murine leukemia retrovirus (MLV)
evolution that delineates where contamination could come from and where it could not come from. You can find it on the Front Page of
the Forums (links are not working today).
- Tripping Up XMRV Too Completely? (from the abstract)- Dr. Bogard from Duke
penned a paper stating that, to put it bluntly, XMRV gets it’s butt kicked by the APOBEC 3G enzyme found in most of our cells
and that’s something of problem because if its getting knocked down in most areas of the body it becomes difficult to figure out how it is causing damage.
XMRV does appears to be more active in prostate cells that do not carry this enzyme and it is apparently these types of cells where XMRV
could do its work.) The authors also assert that if XMRV or other MLV’s had been active in human cells for long that over time they would have
evolved resistance to these enzymes – just as HIV has. In short they appear to be suggesting XMRV is a new entrant to humans and because of
that it’s largely being bottled up effectively in many of our cells by our innate antiviral defenses. XMRV may very well be causing a problem in CFS
but if it is it’s because it’s replicating in a still unidentified other cell in another part of the body.
- Six Days to BWG Committee Meeting (and answers for Phase II of the study? – Dr. Mikovits reported the BWG was trying to finish up
Phase II by the next BWG meeting…hopefully by then we will have a report on their findings regarding the sampling/storage/contaminatiion issues
- American Red Cross Says No to Possibly Dangerous ME/CFS Blood – Citing recent studies suggesting that XMRV may, in fact, really be present in CFS, the American Red Cross banned people with ME/CFS from donating blood. Why does a Red Cross ban of CFS blood make the newspapers? Because, as the Red Cross website puts it “Some four million people give blood—the gift of life—through the Red Cross, making it the largest supplier of blood and blood products in the United States.” The Red The Red Cross Band leaves the FDA and the American Association of Blood Banks (AABB) looking a little isolated, what with Canada, Australia the UK and now the biggest single blood donation organization in the US, all turning their thumbs down on the prospects of people with CFS giving blood.
The Red Cross cited the AABB’s ‘active’ discouragement of people with CFS giving blood by asking people with CFS who are not
‘feeling well’ that day not to give blood but went further, stating that ‘in the interest of patient and donor safety” they will ‘indefinitely defer’
anybody who has been diagnosed with chronic fatigue syndrome.
However the Red Cross will not specifically ask people if they have CFS; instead, if during the general health questioning, if the donor volunteers
that they have CFS, they will not be allowed to give blood (thanks to Jennie Spotila for the clarification). No group in the US has taken the
apparently extreme step of actually asking their blood donors if they have been diagnosed with CFS.
Patient Campaign to Stop Blood Donations….Just Revved Up…hmmm – The Press Release came just a couple of
days after a new patient protest campaignfocusing on getting,
ahem, the Red Cross and the FDA to ban blood from ME/CFS patients got started.
Rivka reported that the Red Cross told her the
decision was made
in October….(but it took a while to write the press release? Whatever happened
patient action does help. Check out Rivka doing some action of her own in the front of the Red Cross
Building in the campaign video.
All the Study Data Fit to Print – the FDA has
released a nice chart of all the published and conference study data on XMRV prevalence. The chart provides
the area study originated from, the type of samples used, the results and the methods used. Thus far, according to
the chart 6 of 13 prostate cancer and six of 14 CFS studies studies have been positive. It does not include some studies
that haven’t made it to the conferences such as the Joliceur study. It does include the Cheney study (even
if they spelled Cheny wrong). The ratio of positive studies drops a bit as they move into other
disorders (2/7) five of which were HIV studies. Except for a few studies with almost 0 results the same ‘find it or not’ pattern
prevails with researchers finding XMRV in both healthy controls and patients or not at all.
- Dr. Cheney Reports – in his latest newsletter – or at least that part of which is available for free – Dr. Cheney reports
news on the serology tests emanating from VIP Dx. Earlier Dr. Mikovits noted that antibody tests picked up more positives than PCR tests.
Dr. Cheney noted that 2 out of the three people who tested negative by PCR later tested positive by antibody tests. Overall 83%
of his 47 patients have tested positive. He expects the percentage to rise to 90% when all the serology results are in – putting the number right about where Annette Whittemore suggested when XMRV broke. It appears from his numbers that the antibody test may add maybe another 10-15% to the percentage of positives.
Rather startlingly Dr. Cheney reports that 60% of family members without CFS also tested positive but the numbers tested were very low (10 ) and therefore could change dramatically. Nevertheless, if they are ultimately validated, they would indicate that XMRV is quite infectious – not a surprising finding given the mostly anecdotal evidence to date; XMRV appears to be a more robust virus than HIV and may be able to survive in the saliva and semen and cervical fluid.
How odd it is, though, that the positive rates VIP Dx reported in its testing of putative CFS patients –
somehow around 50% as I remember- are lower than Dr. Cheney appears to be finding in family members and exposed
controls without CFS (but perhaps with other problems)…or maybe it isn’t ‘CFS’ being such a vague category. Dr. Komaroff reported recently that
a significant percentage of people diagnosed with CFS by primary care doctors don’t appear to have it – thus a certain portion of people that the VIP Dx
may not have ‘it’ whatever it is :). In any case, the high rates of XMRV postive
patients in Dr. Cheney’s practice vs the lower rates in VIP Dx at large are yet another small but perhaps telling validation of the WPI’s initial results because
if XMRV is a more or less ‘CFS-centric’ bug then we would expect higher rates in Dr. Cheney’s practice than in other practices that do not focus on CFS.
What we don’t know, from this short excerpt, is what Dr. Cheney or VIP Dx considers a positive antibody result. When you get to the level of clinical testing – a single positive result is never considered determinative – it’s always backed up another positive test. Dr. Singh in her patent application requires two positive antibody tests for a sample to be considered positive. Determining what combination of tests will, in the end, constitute a true positive is a thorny issue, one that the BWG will have to grapple with at some point.
- Blood Working Group Meeting – Put it on your calendar – Dec 14th/15 – Dr. Mikovits said the BWG hoped to be complete with Phase II by this meeting. Hopefully they’ll be able to meet this target.The Group put together a summary of Workshop that included sections on both the positive negative studies and which included this interesting line….” In contrast to the previously reported findings of close genetic relatedness of all XMRVs in patients with CFS and in PC from different geographic regions the amplified gag gene sequences revealed a genetically diverse group of MLV-related viruses” How odd that the more widespread group had less genetic variability than the localized group….It’s another XMRV oddity, for sure, which presumably has something to do with the different testing methodologies.
In any case the BWG appears to have fully incorporated the Alter/Lo and Hansen studies into their protocols – they are now looking for MLV’s -not simply XMRV.
They are, of course, not alone – the Alter/Lo paper shifted the ground on XMRV – Dr. Mikovits Dec 2nd talk in Norway (what a pleasant place to visit in Dec!) will be on ““XMRV and other MLV’s in ME/CFS”.
The BWG’s conclusion was that everything’s is about as clear as mud – but! – we are working on it.. “The science of MLV related viruses in humans is still evolving. While many laboratories have detected MLV-related sequences in prostate cancer samples, others have not. The frequency of positive samples varies widely between laboratories. There is controversy about the detection of MLV-related sequences in CFS with the majority of laboratories failing to detect MLV sequences. There are ongoing studies to determine whether technical issues, such as extraction methods or primers and/or subject selection including clinical criteria and geographic issues might influence the detection of MLV sequences.”
Of course we expect clarity and are disappointed (and worried) and if its not forthcoming. In a recent Newsweek article Dr.. William Schnaffner, an infectious disease specialist, suggested that we should neither expect clarity at this point or be disappointed that it has not appeared ““Cutting-edge science is often not definitive,” says Dr. William Schaffner, an infectious-disease expert at Vanderbilt University School of Medicine. “Keep your seat belts tight.”
- That Newsweek Article – is empathetic and well-written and well worth reading. In it Dr. Andrew Mason, after referring to the battle over decades long battle over the cause of ulcers, argues that anti-retroviral trials are the ‘the only way to win this battle’. Dr. Lipkin would not agree stating “Patients are clearly ill and suffering, and we need to address treatment as rapidly as we can. But the first order of business is to determine if the association is real.” Dr. Lipkin is clearly intrigued by ME/CFS – he is engaged in two studies – but it took the NIH almost a year to get his study off the ground – hardly a sign that they’ve been working as rapidly as possible. Still, when they did get into gear they did so in big way – hiring one of the top pathogen detectives to lead the search.
- Dr. Deckoff Reports – http://treatingxmrv.blogspot.com/ – meanwhile Dr. Deckoff and her daughter continue to slowly improve. It’s not dramatic..it’s slow drips over time that she notices over the months rather than the days. They are charting functionality using the Karnovsky Index and both have pushed past 80 for the first time. One of the surprising benefits for her has been a reduction in peripheral neuropathy (nerve pain) that can be very painful.
- Test Results – meanwhile there have been a flurry of test results on the Forums. Several people received positive results by culture and negative results by serology at VIP Dx – rather the opposite of what one might expect at first – but perhaps suggesting a poor immune response to the virus (or an antibody test that needs some improvement). Another person with milder CFS (myself) tested positive by culture (it took a long culture) – suggesting that viral loads were really low and I but had a strong antibody test – which I was told could be protective (which might be why viral loads are so low???). I had gradual onset and Dr. Mikovits noted that others with gradual onset have tested positive. There appear to be several different variations and the science, of course, is still evolving…… One of Dr. Peterson’s patients who tested positive by WPI tested negative by Dr Jay Levy – a virologist who was associated with CFS in the early days.
- the Buzz at the Blog -The Buzz
will now available on the
Bringing the Heat’ blog, – and this is the correct addess..:) –
you can subscribe to it and get it in your email if you wish and it will be uploaded to my Facebook page as well.
- The Singh XMRV Patent – The Next Cancer for XMRV? Breast Cancer, Prostate Cancer Results Validated….CFS still Unclear The Next Cancer for XMRV? – JMK on the MECFS Forums snuffed out Dr. Singh’s XMRV patent application and then XMRV Global Action highlighted the most relevant sections and here we are with what is easily the most exciting news for XMRV since the Science paper was published in October of last year. The patent application states Dr. Singh has found XMRV in 25% of 178 samples from patients with breast cancer – a finding that will surely send a shock through Cancer research community. Tellingly, XMRV was not found in the tissues just surrounding the cancer as originally appeared with prostate cancer – it was found smack dab in the middle of the malignant breast tissues.
Hormones plays a role in many cancers including prostate and some breast cancers…is XMRV, which we know has a hormonal connection, zeroing in on hormone related cancers? Studies change the course of research efforts not patent application but it’s a patent application from a respected and careful researcher and you can bet your boots several papers on their way….
Prostate Cancer Clarified – breast cancer wasn’t the only cancer to get a big hit. The XMRV prostate cancer connection has been questioned because of the inability, thus far, to find XMRV in the malignant tissues themselves – it’s always been found in the tissues just surrounding those tissues but no longer; the application, rather startling, stated that these new immunohistochemistry and antibody results indicate XMRV is overwhelmingly found in the malignant epithelial tissues in prostate cancer patients. If validated, this will, undoubtedly ramp up XMRV cancer research efforts.
Happily the antibody (30%) and immunohistochemistry (27%) results correlated very nicely – thus providing an important check on their validity. The immunohistochemistry staining also revealed a telling pattern of XMR positive cells clustered together – just as you would expect with a virus.
Still an Underestimate – interestingly Dr. Singh believes her tests still underestimate the prevalence of XMRV in prostate cancer because it’s found in such a small subset of cells and that a closer examination of the tissues. will most likely lead to increased prevalence rates. Viral load is believed to be very low, in fact, she believes it is “close to the detection limit of the qPCR’ assay.
She doesn’t appear to have much doubt about the potential virulence of the pathogen, though; her results showed that XMRV presence was a correlated with cancer severity; that is, the more severe the cancer the more likely it was that XMRV was found in it.
More Cancers?/More Tissues? – Findings of other cancers were not detailed but the application does appear to indicate (?) XMRV was found in
immune cells in the lymph nodes, the bone marrow and peripheral blood from hematological malignancies as well as the testes. (This is in a section that lists ’embodiments’ of the present methods). Hematological malignancies refers to cancers that affect blood, bone marrow and lymph nodes and include such cancers as leukemias and non-Hodgkin’s (and other) lymphomas. Non-Hodgkins Lymphomas are reportedly found in 5% percent of Dr. Peterson’s Nevada cohort.
The immune cells in the lymph nodes could be very telling as the lymph nodes are a reservoir for many infections. It seems likely that these results could reflect the autopsy work Dr. Singh has been doing. On the other hand, the application did state that the only other tissue XMRV was found in the 8 prostate cancer patients she autopsied was the testes.
XMRV Clarified – Dr. Singh has gone a long way in refining her techniques to find the virus. First she generated a new infectious clone called pXMRV33 constructed from two overlapping clones. She transfected some cells with her clones and nine weeks later began to detect reverse transcriptase – an enzyme associated with retroviruses. She then took the supernatant (cell free material), dropped some cells in it and then was able to detect retroviral activity in cells – indicating she had an infectious retrovirus on her hands.
Electron Microscopy -looking through an electron microscope she was able to see abundant viral particles that resembled a murine retrovirus.
Antibodies – she was able to find antibodies specific to XMRV by affecting rabbits with it and then doing Western blot tests. She found that (except for the env proteins) the amino acids in the proteins associated with XMRV were very similar (90%) to those in the Moloney murine retrovirus she’s been studying for quite some time.
It appears that she has replicated several important aspects of the WPI study and in at least one way has added to it; she has demonstrated that she has an infectious virus, she has created PCR and antibody tests whose results, at least in prostate cancer tissues, correlate with each and her electron microscopy results suggest she has a MLV-like retrovirus. Plus her immunohistochemistry test provides a newway to validate her results.
XMRV In Fluids
Dr. Singh has also refined her testing protocols for many of the bodily fluids. The application states that her immunohistochemistry assay, in fact, can be used to
detect XMRV in saliva, semen, peritoneal fluid, synovial fluid, prostatic or cervical secretions, blood and serum. It describes a specific method for finding XMR in
cervical fluid – and notes that the potential for spread from mother to child via that means.
Semen Findings Validate WPI Findings for Healthy Controls – – The XMRV in semen finding had important implications because XMRV showed up in the semen in exactly the same percentage (7%) of healthy controls as tested positive in the original Science study
– a very nice validation of the WPI’s original findings. Dr. Mikovits long ago, if I remember correctly, stated XMRV was found in the semen but Dr. Singh is the first
researcher, I believe to validate Dr. Mikovits statement. The semen, of course, have significant implications for the possibility of transmission.
Chronic Fatigue Syndrome – The juice seemed to run out a bit when it came to ME/CFS, however. She has definitely made progress; the application states
2 XMRV antibodies have been found in a CFS patient and that most of the ‘non-reactive’ samples came from the healthy controls.
Dr Singh also knows which XMRV antibodies to test for (SU, p15E) and which ones not to test for (CA – found in healthy people as well). We can guess that XMRV showed up more consistently in CFS patients than in the healthy controls – a nice start! – but we don’t have any idea of what percentage of people with CFS she found it. It looks like
we will have to wait for her paper for that.
- DecemberDate for Phase II? – I asked Dr. Mikovits when she expected the Phase II of the Blood Working
Groups effort to be complete? She said they hoped it would be complete by the next meeting of the
Blood Advisory Groups – which is Dec. 14th
- The Race Is On – In her latest blog Amy Dockser Marcus states that researchers are ‘racing’ to develop
tests for XMRV.
Abbot Diagnostics, Gen Probe and Roche Diagnostics are hard at work and Roche says it believes it will have a
test for researchers available in months. Gen Probe, on the other hand, is developing a test to detect an early warning
XMRV test that can find XMRV after infection but before the immune system starts producing antibodies. The Cleveland Clinic,
meanwhile, is developing a test that can find XMRV in the urine.
To get beyond the ‘positive specimen controversy’ that cropped up when
the CDC was unable to find XMRV even in the samples the WPI had stated for positive, researchers at Abbott, Cleveland
Clinic (which was part of the original study…) and Emory University are creating positive samples by infecting
monkeys with XMRV.
The Antibody Tests Antibody test development is a hot item. Abbott, Cleveland
Clinic and Emory together and Dr. Singh, working at ARUP labs, have each developed antibodies to three proteins
on the virus. Dr. Bagni at the NCI has developed a test that is deemed positive if it reacts with (yes) three
antibodies. (A positive result to an antibody test often requires that a person test positive to
more than one antibody).
Now all they need to do is find it in ME/CFS.
- the Buzz is Moving Up in the World – suddenly, 10 months or so into the
Buzz, the light bulb went on and I thought…hmmm
why not take advantage of some of the capabilities of the internet? The Buzz
will now be available on the
Bringing the Heat’ blog, as well –
you can subscribe to it and get it in your email if you wish and it will be uploaded to my Facebook page as well.
- Unbroken – the Louis Zamperini and
Laura Hillenbrand Story – no it’s not about XMRV but it is about Lauren
Hillenbrand and that means CFS. She is a great spokeswoman for CFS and Louis Zamperini was a great vehicle for her
next book, seven years in the making and which she says both brought her life and cost her physically.
- A Mouse Model for XMRV – And now to one of the more interesting twists – developing a mouse model
for an er…mouse derived virus? Of course we now know that XMRV does not appear to be found in the mice much
(if at all) either in the wild or in the lab (which does kind of make one wonder how it managed to contaminate
the WPI’s samples……if the worry was contamination from lab mice and it’s not actually in lab mice….then how did it???? Never mind)… the key
with this study is that researchers have found a mice they can manage to infect XMRV with (it wasn’t easy),
and now that they can do that they can make them ill, probe them, dissect them, feed them drugs, whatever….essentially the way
is clear for the magnificent animal research establishment
to go to town.
Thus far they’ve found XMRV in the spleen (expected immune organ), the blood (naturally) and the
brain (most interesting)..(If mice have prostate glands and it was found in them they didn’t (perhaps out of respect for
their privacy) report it was found there). The mice did recognize XMRV as something not good and did amount an
immune response to it. Like humans their immune cells were able to knock it down with their all purpose XMRV
transfiguring APOBEC enzyme…and that was that…..Now about those brain cells……where and what kind???
- Dr Enlander Talks – Dr. Enlanders comments on the muddled state of XMRV thus far.First he provides an insiders view
on what we can now see was a very hastily done first followup study that appears to have broken speed records for study
approval, completion and publication (thus implicating an nice swath of the UK CFS medical establishment in a rush to judgment…
wouldn’t they have been smarter just to wait a month or two? Somehow they didn’t mind that everyone
else would be agog at their ability to manipulate the process -which, come to think of it, may be the most telling
thing – that they just
didn’t mind ….Where would we be without the British?
He notes the both the differences and the close association between XMRV and the
MLV’s found in the Alter study – a tricky and still unresolved subject and notes some shortcomings on the pro-XMRV side; despite it’s
the first study had some of its own, ahhh, issues (and how unbelievable is it that here we are, a year later, talking about the
first study….) and the WPI’s
lack of receptivity for whatever reason (and we have no idea, so let’s not even speculate) regarding his own proposed double-blinded XMRV study.
He ends by
noting something most ME specialists (and all patients) would probably agree with “All of us would love to initiate treatment’ – and let’s leave it at that.
He is reportedly currently
at work on a double-blinded XMRV study using multiple labs.
“I was asked to comment on the XMRV research.
In Oct 2009 a virtually unknown Institute in Reno, Nevada, the Whitmore Peterson Institute, published in Science exciting
research in which they claimed to have discovered a new relationship between the XMRV virus and CFS/ME.
This was exciting news, we hoped it was the initial foundation of proof, that CFS/ME was a physical disease.Within 6-8 weeks, miraculously, papers were in publication denying the original research. Usually it takes my Medical
Center several weeks to allow a research proposal to proceed, followed by several weeks or months for the research to be
completed and then several weeks or months for journal acceptance and publication. So I was astounded, as were others,
at the time frame of the response, the journals and the relationships of the publishing research centers.
Then a virtual boxing match occurred. This was to the detriment of all. One institute claimed poor cohort selection,
another bad specimen handling, another claim related to lab contamination , stale samples that were stored for years,
one even blamed the Chinese company that made the specimen tubes and so the complaints and cross complaints mounted.
Harvey Alter, a research physician at NIH of ultimate repute, showed that indeed there was a MLV virus in CFS/ME specimens.
This was countered by statement that MLV did not replicate the XMRV virus research. In essence this is true but
the MLV virus and the XMRV virus has similar virion particles and/or cross reaction. Instead of certain research
workers blasting this difference, it would have been opportune to investigate the relevance of the presence of either
of these virions.
Both the protagonists and antagonists are not flawless. The initial research was not replicated in
a double blind, multiple lab replicate study by independent selection.
I offered, Whitmore Peterson, an independent replicate study of carefully selected Fukuda/Canadian criteria
patients and controls between five viral labs. They were not interested. The whole matter of this research is
puzzling, agenda seems to overpower the research . All of us would love to initiate treatment, if indeed the virus was causal and if the treatment neutralized the virus. Lab research into non toxic neutralization in cell culture is incomplete and must be performed prior to using toxic anti-retrovirus treatment in patients. Action against XMRV should be explored in vitro of existing non toxic anti-CFS/ME methods viz; Ampligen, Kutapressin, Nexavir, Hepapressin, isoprinosin etc.
In future I hope to see a united effort in exploring this devastating disease rather than a continuous boxing match- news that even our Utah XMRV/MLV expert was finding XMRV more complicated than expected
- Amy Dockser Marcus recently told us that Dr. Lipkin called together representatives to discuss his study about 2 weeks ago.
Now we’re getting a few telling details – or rather we can infer a few telling details. She notes that clinicians from Miami,
Boston, Palo Alto and Salt Lake City will be involved which can only translate to four of our top physicians: Dr. Klimas, Dr. Komarroff,
Dr. Montoya and Dr. Bateman. (Do you think they know a person with CFS when they see one?)
Dr. Lipkin will be taking a broad sweep
of the viruses – looking for XMRV and all over viruses in the same family. Patients will have to meet two criteria, which
given the physicians involved, can only mean the Fukuda AND the Canadian Criteria PLUS they will have to have
infectious onset which means the patient cohort will closely duplicate the original patient cohort in the Science study – which is,
of course, what we want. Three labs will test the blood -the WPI, the FDA/NIH (Alter/Lo) and the CDC.
ME/CFS experts providing ‘good’ ME/CFS patients
and using two of the only labs to actually find XMRV? This looks like an excellent study.
Now how about a timeline?? :):)
- It’s Not a Passenger Virus? – I missed it but Dr. Vernon’s take in the last CFIDS ELINK was intriguing. She wrote ”
Possibilities for XMRV being opportunistic or a passenger virus seem to be narrowing based on the negative
results in cohorts of patients with immune suppression, immune activation or blood-borne infections”. What an interesting
statement this…..and it makes sense – if XMRV is not in patients with immune suppression then it’s not likely to be a
passenger virus in CFS either is it? (This conclusion, of course, requires that HIV/AIDS researchers are looking for it correctly).
If Dr Vernon is right, then if XMRV is found in ME/CFS then it is exploiting some sort of abnormality unique to it – which brings
up the possibility of having a retrovirus found in CFS, Fibromyalgia, autism, etc….but not in immunocompromised AIDS patients
which would very be different indeed.
- No Surprise – news that even our Utah XMRV/MLV expert was finding XMRV more complicated than expected
probably should have come as no surprise…broken timelines have been maybe the most consistent thing we’ve been
able to observe with XMRV. Consider these
(*)WPI, with Glaxo Smith Kline reportedly on board, was reported to expect treatment trials to begin within six months of the Science publication.
(*)At the CFSAC meeting late last year Dr. Coffin thought we’d have the answer ‘within six months’
(*)The antibody tests were promised and promised….but eventually they did arrive (so there’s hope :))
(*)The WPI started with one set of methods in the Science paper and then brought forth an improved set about five months later
(*)Dr. Singh’s study is taking a bit longer than expected because – a PR Forum member was just told -it’s more complicated than expected
(*)Dr LeGrice and Dr. Glynnis just a month ago thought Phase II would wrap up about 10 days ago….
Who wants to bet on Phase III being wrapped by New Years? XMRV is clearly complicated. It’s definitely past time to stop expecting anything to happen on a
timeline. All we know for sure is that the results won’t be done until they are done – and not a second before.
- International Conference
Rita on the PR Forums somehow found some interesting XMRV abstracts in the 11 Symposium on Antiviral Drug Resistance – demonstrating
again that XMRV is getting in anywhere it can.
XMRV in Immune Cells – One from the National Cancer Institute sought to explain an interesting dilemma – research done after the
WPI’s Science paper indicates that XMRV is basically knocked down and rendered non-infectious by the APOBEC3 enzyme in the immune cells in the blood
the WPI found it in. (The amino acids the enzyme replaces in XMRV makes it impossible for XMRV to replicate.) Yet after digging
XMRV out of these immune cells the WPI was able to grow the virus and replicate it! If that enzyme had rendered XMRV inert,
so to speak, how was the WPI able to get it to replicate again? These researchers found that XMRV could replicate in PBMC’s
only if the APOBEC enzyme was inactivated. However, if they cultured the cells with ‘canine indicator cells’ they could recover
infectious virus. This suggests to me, a laymen, way in over his head, that there are substances that can help XMRV bypass the
However, these researchers suggested that this does not happen in the blood in the body, and that
at least as regards replication, the immune cells tested thus far
are essentially a dead end for XMRV. (Hence the search for a different viral reservoir)
One of the most interesting part of this study was the ease with which they did it. They simply infected
cells with XMRV and monitored virus production using quantitative PCR. It’s clearly much easier to purposefully infect
cells and then detect the virus again than it is to find it in the blood.
Dr Coffin Gets Down to Work! – Dr. Coffin’s at Tufts and the National
Cancer Institute (again) have been taking on one of
thorniest problems – how to distinguish XMRV from mouse DNA or from an endogenous retrovirus.
An endogenous retrovirus
is a retrovirus that, sometime in the distant past, inserted parts of itself into the genome of an organism.
The genomes of inbred mice in labs, in particular,
are swarming with degraded non-infectious MLV gene sequences. The right bit of mouse DNA contaminating a sample could,therefore, look like
XMRV. The WPI was able to isolate the whole virus – indicating they did not discover an endogenous retrovirus – but no one
A very specific PCR assay Dr Coffin developed for XMRV has not found it all in inbred or wild mice – suggesting, as Dr. Mikovits
reported, that it is unique to humans. They developed another assay that distinguishes between XMRV and endogenous MLV retroviruses – thus
enabling them to quickly tell if a gene sequence belongs to XMRV, an endogenous retrovirus or from mouse DNA. Plus
they’ve developed another PCR assay that focuses on mouse ‘DAN’ contamination.
It appears that researchers are becoming
ever more effective at determining when an XMRV result is real and when it actually reflects something else. These tests will be
be very helpful (a) to researchers such as Dr. Alter and Dr. Hansen who have found gene sequences that are XMRV-like but
have pMLV characteristics and (b) to clearing up the contamination question. Basically it appears Dr. Coffin now knows XMRV when he finds
- Some Light on the Singh Study – the Singh study is big (@100 patients) and comprehensive – besides doing culturing Dr. Singh
she is using two kinds of PCR and for viral RNA and presumably an antibody test. The blood storage, etc. protocols
are the same in both the healthy controls and patientsAND they are all from one area (no geographic sequence
variation). Plus Dr. Singh has been studying XMRV and MLV’s for years. In short it’s quite an
Slippery Beast – I asked Dr. Light, one of the principals in
the study, if there was anything he could say about it? He reported they just had a meeting – they think the are,
as he put, ‘finally getting a handle on it’ but are still not sure – and they didn’t want to build up hopes
one way or the other. He hopes they’ll have something definitive to report soon.
XMRV, no surprise, given the ups and downs of the past year,
has been a bit slippery. The Singh study began early this year – it’s probably somewhere in
its 7 or 8th month now. One grace of Dr. Singh’s study (and a complicating factor) is its complexity; she will
want the results of the different tests (2 PCR’s, RNA, culture (and antibody?)) to agree – not an
easy task with a relatively new virus. Of course, when the different
tests do all agree then you have a really solid result.
For more on her study click here.
XMRV is certainly in good hands; Dr. Singh is pushing the field forward in several ways. She has developed
an antibody test and her own XMRV clone and, of course, is a key player in the XMRV prostate
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- The Phase II Dustup Campaign Continues – patients upset with the Blood Working Groups
reluctance to keep a ME/CFS Community, that’s sitting on the edge of its collective seat,
of the progress of their work, now have a place to go. Otis on the PR Forums has created a nice
website with names and numbers to email. The BWG may not be able to release the
results now but they can certainly be more forthcoming. Check it out here
- Blood Working Group Responds – A Little – almost a week after emails were sent out requesting the status of the BWG’s findings
Dr. Holmberg, the co-chair of the group, did respond. After a rather pro-forma beginning – this is what we’ve done – see how public we’ve
been thus far, he ended with a pro forma response – Phase II is not done yet.
Thank you for your inquiry regarding the activities of the Blood XMRV Scientific Working Group
which was received both by Dr. Glynn and myself. The mission of the Working Group has been reported at several venues.
The methodical process has been tracked in various phases, phase I-IV. The results of phase I are available and have
been reported at the first XMRV Retrovirus Workshop (http://www.virology-education.com/index.cfm/t/1st_International_Workshop_on_
XMRV/vid/1FF10297-0DC4-5841-64634A68A3EC3EF1). Phase II required institutional review board (IRB) approvals and consists of
pilot studies to evaluate how to best decrease the variability in sample preparation. As a result, Phase II is in progress and
there are no results to report yet. We will report results when available.
Is that enough? I don’t think so. Would providing a general timeline be too much? If it’s probably going to take another month or so then
why not state so and
let everyone relax? The BWG (and other) federal groups don’t realize how far a little bit of good will goes (or how much frustration has
built up over the years.) Dr Mangan, the new head of the NIH effort on CFS, God bless him, does get it. Hopefully the BWG will as well
has been asked to provide a general timeline.
So what are the facts thus far? We know that on Oct 14th Dr. Glynnis, the co-chair of the Blood Working Group stated that she thought
the results would be ready in just three weeks. That suggested that the group was, more or less, wrapping things up and that the end
was in sight. Now they’re about a week overdue – no big deal. A couple of more weeks of no results would suggest, though, that either
a) the first estimate was never close or b) something unexpected occurred. I would guess B. Dr. LeGrice, after all, gave that same three
week figure as Dr. Glynnis did and officials associated with the program have been talking about XMAS/New Years as the end date for the NEXT phase.
Time will tell.
- ‘Project Groundswell’ Starts – author and advocate Peggy Munson starts Project Groundswell to stimulate ACT UP-like actions
to raise awareness about ME/CFS and force accountability from the government. Check it out here –
- The Stars Begin to Align: Good News for the WPI and Other CFS Researchers – a huge hurdle for CFS researchers has somehow recently been removed. After Charlotte and Bob
somehow dug up the latest Grant review panel (CFS SEP) for CFS (it’s incredibly hard to find) they found, surprise of all surprises, that it not only that
actually contained mostly CFS researchers but that it contained quite a few contained immunologists/pathologists.
The WPI’s difficulties obtaining grants
aren’t limited to them; many researchers have had difficulty getting their grants funded. One of the big reasons for that
was a CFS SEP review panel that has over the past decade been dominated by pain and, believe it or not, dental researchers. That has all
changed; CFS researchers can now look forward to having their grants reviewed by the likes of Dr. Klimas, Dr. Ruscetti and Dr. Friedberg. This should
mean better grant scores and more funding for CFS! Check it out in The Start Begin to Align for ME/CFS at the NIH
- An Ally in Unexpected Places – the Rutherford Medal is the top medical prize in New Zealand and the man who just won it knows CFS well;
his daughter has had it for 20 years. In an audio interview Dr. Tate called ME/CFS a ‘devastating disease’ and spoke of his ‘tremendous respect’
for people fighting the disorder and noted that at one point all his daughter could do was to crawl to the shower.
He called it a disorder in which the innate immune system is permanently switched on. His daughter came down with ME/CFS after a
bout with EBV (infectious mononucleosis, glandular fever). He is eagerly awaiting the outcome of XMRV and suggested that the EBV infection could have
created the environment
that allowed another virus (such as XMRV?) to enter. (If only he ran the NIH……) Thanks to Overthehills on the PR Forums for digging this up. The CFS
portion occurs about 12 minutes in.
- American Association of Blood Banks October Conference – discussed several facets of XMRV including the Canadian decision to not allow
people with CFS to get blood, the ‘variations’ of XMRV (interesting….), a South African study finding no
XMRV in HIV infected individuals, a presentation by Dr. Mikovits and Dr. Ruscetti about the effectiveness
of the Intercept system for inactivating XMRV and an antibody test for XMRV by Abbott labs.
Thanks to Bob Miller for providing this.
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Check it out here.
- The Patient Community Twists and Turns and the Blood Working Group Remains Mum
A month earlier Dr. Glynnis at the CFSAC panel Oct 14th (1:45:28) stated
“We hope we’ll be able to have results of this ongoing study by early November and it is our plan certainly to immediately release the results because we think they will be extremely important to the scientific community
….so that the optimal preparations of the samples will be known.”
Amy Dockser Marcus’s blog in the WSJ stating that Dr. Lipkin, who is reportedly going to
use BWG findings for his study, met with federal officials, researchers and advocacy reps to discuss how his study
will now proceed, of course, set off a firestorm of speculation. Was the BWG done? Why have a meeting if it wasn’t?
If it was, why not release the results?
That the details of that meeting were embargoed meant what? Speculation raged…was this good news or bad news?
CAA Board Member
Jennie Spotila was willing to jump in and state that, while she wasn’t privy to all the information, she thought the BWG findings had nothing to do with Lipkin’s
The only thing certain
is that the federal officials have once again allowed events
to spin out of control in the patient community, leading to more and more speculation and, of course, anxiety. The CAA
is caught in the middle between their promise to keep the information embargoed and a community that would like to
know what’s going on.
The BWG could easily clear up the confusion but repeated emails to the BWG co-chairs have been ignored.
Perhaps the most logical assumption to make at this point is that Dr. Lipkin just happened to call his meeting about the time
that the BWG was to release their results and that the BWG, as have most groups in the past, is just taking longer than
expected to finish up their study…..and that they’re simply inept at dealing with a curious and informed patient population.
– things appear to be going well for Dr. Deckoff-Jones and her daughter, Ali. Eight months into
their anti-retroviral trial, Dr. Deckoff-Jones reports that that recovery is ‘incomplete’ but their ‘improvement feels pretty solid’ with their
worst symptoms gone or hugely reduced. Basically she says “its a life”. Ali is taking interest in typical teenage
girl subjects (she’s writing a post apocalyptic vampire novel). Dr Deckoff says she is ‘living and
breathing her subject right now’ which taken literally could be a little scary but is another good sign of
Dr. Deckoff-Jones again mentions ‘Actos’ – an anti-inflammatory and glucose metabolism regulator. With the sensitivity to
sugar and the inflammatory symptoms present in ME/CFS the supplement seems almost like a no brainer. There’s more in the blog on Actos
and its properties
drugs in people with CFS who choose to use them in The Tuskegee Mentality: Condemning Antiretroviral Treatment for Chronic Fatigue
6 DNA defects that could make people with ME/CFS more susceptible to viral invasion – a tack that Ian Lipkin appears to be
taking with autism; it’s not just the virus – it’s the viral – genome connection that confers disease.
She reported XMRV
is more easily detectable in the cell free blood plasma than in PBMC’s. Viruses, of course, infect cells, replicate in them and
then travel through the plasma looking for more cells to infect.
In the background info she noted the RNase L and NK cell abnormalities
in many people with ME/CFS which could decrease their ability to fight off pathogens. (Interestingly, early Dr. Mikovits reported
that XMRV infection was not associated with either of those measures; instead it was associated with interferon levels. Earlier she also
reported that she had found an immune signature in XMRV positive patients; that paper will go a long way towards clearing up the
what immune abnormalities are associated with the infection. However, that paper probably, one would guess, will not get
published until the research community has come to a consensus on XMRV.
Dr. Mikovits explication of the MLV’s effects on mice was almost painful in how it closely matches some ideas regarding
CFS. She noted how MLV’s tend to replicate in the epithelial cells lining the blood vessels in the brain, which activates neuro-glial cells
causing them to produce pro-inflammatory cytokines resulting in ‘leaky capillaries’, inflammation and neural damage.
fascinating spinal fluid proteome study findings suggested a very similar scenario; increased inflammation (associated with amyloid
factors) that stick to and puncture blood vessels causing leakage (and more inflammation). There is also intense interest in
the role neuroglial cells play in producing pain in FM and other mysterious pain disorders. Plus virtually everybody, it seems, is
interested in the role cytokines produced in the brain play in CFS. Cytokines, for instance, trigger ‘sickness behavior’
which is nothing more than a weird way to refer to the fatigue, pain and other fluey symptoms associated with colds. Even the CDC
is very interested in the role Interferon plays in CFS (ironically enough – it’s a cytokine Dr. Mikovits associates with XMRV). So there’s alot
of potential overlap between the damage Dr. Mikovits reports MLV’s cause and findings in ME/CFS. Thanks to Andrew for providing a friends summary of the event.
Dr. Baraniuk’s followup brain proteome study is
finished and my sense, in talking to him, was that results were good’. A validation of his first paper would be a huge win.
- The ‘Big’ (Little?) Lipkin Meeting – did occur. It does appear to have been focused on Dr. Lipkin’s study. Why federal, research and advocacy representatives or invited to it is a question whose answer we will presumably get at some point. Since the Lipkin study is using the Blood Working Groups findings we have to assume that they have come to some conclusion about storage/sample preparation/contamination, etc. yet for some reason we’ve heard nothing as the contents of the meeting have apparently been embargoed…which means what? Big news? A really secretive researcher? Is the BWG waiting for
- Three compelling fundraising video’s from the Whittemore Peterson Institute. Stating “As far as I’m concerned the WPI brought us out off the darkness into the light” Dr. Jamie Deckoff-Jones at times emotionally relates the difference the WPI has made in her and her daughter’s life using treatments based on the WPI’s XMRV findings.
Another video features parents of children with a different neurological disease. The last was the most compelling for me; it features a father who
used the WPI’s technology to find three viruses in his daughter – who almost overnight was able to speak coherently for the first time using antiviral therapy and goes on
talk about the importance of private funding.
- Never Easy – The Singh’ Study Proceeds – The Singh/Bateman study appears to have wrapped up but like just about everything else in XMRV the data does not appear to have come easily. Patients were first told to expect results in July/Aug (remember Dr. Bateman’s webinar in which she hoped to be able to present some results?) now it’s November and they’re still waiting.
the right time (whatever that could be?) Who Knows? The ME/CFS community was promised, however, a quick release to the BWG’s findings – and that has not occurred.
- Big Meeting? What Big Meeting? On Thurs Amy Dockser Marcus in her blog at the Wall Street Journal
noted that Dr. Ian Lipkin had convened a meeting of federal, academic and advocacy representatives
to discuss the next phase of the search for XMRV. Now that the Blood Working Groups findings
APPARENTLY are in (contamination/no contamination, proper sample preparation and storage) he is due to
kick off his own study using those findingsl.
But why would HE call these
groups to New York to discuss the ‘next stage’ of the search for XMRV in CF’? He did not produce the findings, nor is he
slated to lead a broad effort on them – he is, so far as we know, involved in one, admittedly
quite large and important study, but nevertheless, just one study on XMRV and CFS. So why is HE
calling these people together? Will a broad new effort take place? What is going on with this
meeting – that apparently has taken place according to Amy, yet we’ve heard nothing about it. The questions
Like so much else in XMRV the process continues to surprise!
Can we make anything of the fact that the effort to find XMRV will shift to the ‘next phase’? Does
this mean they’ve ruled out contamination? It could but it might not as well – it could just mean
that they feel confident that they know how to search for XMRV now and they are starting afresh and resampling
or newly sampling people with CFS. The
definitive assay for XMRV, by the way, is not due until around the New Year – this meeting seems to be
about the ramifications of the BWG’s findings and gathering samples for the definitive studies.
- Website Teetering – First the website was down – then it was up but I was unable to publish to it. Now I
appear to have found backdoor approach to publishing. It may not be pretty but it seems to work and hopefully it will remain open.
- The Big Headscratcher – Looking back one of the big headscratchers
for the Blood Working Group must have been the CDC study. It wasn’t the results
of the study but what preceded it – the CDC’s attempt and inability to find XMRV
in the XMRV positive samples the WPI sent them prior to the
publication of the Science paper. ‘Contamination’ seems to be the talk of the
town in some quarters but if there was a contaminant – either XMRV or something
bit of mouse DNA – then the CDC should have picked it up using their oh so
sensitive tests yet they picked up nothing. Dr. Mikovits later said that their
probe was based on an XMRV clone that had been cobbled together from gene
sequences found in prostate cancer derived tissues but they also looked at
broadly conserved sequences for MLV’s and found nothing. Here may be where the
sample preparation questions began to come into play. It’s possible that those
samples did contain XMRV when they left the WPI and didn’t when the CDC put them
into their PCR.
- Website Knocked Down Temporarily – I wish I could say it was a virus
but it was something much more innocuous.
- Big Meeting in New York: Take a Deep Breath- XMRV’s Time is Almost Here: – Amy Dockser Marcus reported that “W. Ian Lipkin,
the Columbia University-based virus
hunter tasked by the government with resolving some of the XMRV questions, is convening a meeting this week.
Representatives from HHS and the academic and advocacy communities are in New York to develop a strategy
for a study to determine whether XMRV is found at higher rates in CFS patients.” Dr. Lipkin is to use the findings from the
Blood Working Group to inform how he does his own study – but this is apparently bigger than
a single study. Dr. LeGrice said about three weeks ago that the blood
storage/contamination issues would be cleared up in three weeks. He was echoed
by the NHLBI rep in her testimony at the same meeting. Now we have
representatives from the government, research and advocacy organizations meeting
sometime this week, which means, given that her blog was on Thursday that it has already
- Dr. Singh on Detecting XMRV – the title of Dr. Singh’s commentary in the Viruses journal
went right to the heart of the matter. The problem right now is a simple one;
“Detecting Retroviral Sequences in Chronic Fatigue Syndrome”. That’s the whole
ballgame – that’s all that anyone cares about right now – its ALL about
detection – this was a timely article and it was nice to see someone tackle this
publically. Dr. Weiss’s Rumor Virus article gave a good historical overview of
the sometimes extraordinary difficulties pathologists can face now given the
immensely powerful technology available to them but Dr. Singhs article actually
delved into the specific issues surrounding XMRV.
Splitter or a Lumper? Dr. LeGrice and others looked narrowly at the pMLV finding
and stated that, until we know more, they should be treated as unrelated finding
– which has its own logic. Dr. Singh
took a broader view and stated the opposite; both have their own logic. For Dr
Singh, considering that the pMLV’s and XMRV share 95% sequence similarity
sequences, the same receptor and, get this, are actually closer to each other
than different variants HIV (85-95%), it appeared it was easy for Dr. her to place the pMLV findings by Alter/Lo firmly within the context of the Science papers XMRV finding.
It’s all about emphasis.
One Big ‘Happy’ Family? Is Dr. Singh implying these are
all one family of of viruses that interact with each other like HIV does? Dr.
Mikovits hinted, if I remember correctly, that more than one type of virus may
be needed for them to survive in the body and Dr S. Ruscetti is reportedly
looking at how these viruses combine with each other. There is also section of the pMLV’s that we know can
jump into other viruses…Are the pMLV’s and mPMV’s and XMRV’s all one family????
Contamination – Dr. Singh felt contamination of the Lo/Alter samples was unlikely because the instruments used to
search for it were 100 x’s more powerful than those used to look for XMRV and the wide discrepancy in prevalence
between the healthy controls and CFS patients. She noted, however, that with the exception of the 8 samples
from present day patients that samples for most of the controls and patients were
handled differently D) evidence of a replicating virus using antibody tests or actually finding the virus are critical E)
(The same thing applies for the original Science study)
The ‘Perfect’ XMRV Study – But how to do a study that helps to clear up the confusion? That, according to
Dr. Singh is certainly doable (and not easy) and definitely has not been done. That study needs to (A) collect blood from a large # of
healthy controls and patients from the same area using the same techniques (B) the investigators must be blinded
(a horrible fate but if it’s necessary, it’s necessary the Alter/Lo study researchers were not and the WPI study did not
report it was in the Science paper) (C) negative controls on XMRV should be checked for contamination prior to amplifying
the samples (D)detailing the limits of detection is important E) replicating one element of the positive study using blood
from positive patients collected by a phlebotomy lab.
Note that Dr. Singh does not believe that it’s necessary to replicate every procedure
from the first paper – one is enough.
We can guess that Dr. Singh’s XMRV study probably (:)) closely replicates her advice and we can get prepared for
a very precise methodological section – probably the most comprehensive yet as she details exactly what she did
and didn’t do – which is what the National Cancer Institute, in fact, is asking XMRV researchers to do right now.
Dr. Singhs autopsy study should be at the publishers now and her XMRV study is
believed to be finished as well. Hopefully we will hear from her in another
scientific journal soon.
- Sample preparation? – the emphasis now is on ‘sample preparation’ with Dr. Mikovits
reportedly stating that may be the major issue. Consider this, though; Dr. Peterson was
able to dig up an XMRV positive sample in a sample that had been stored in his freezer for decades. The ‘Peterson’
samples collected over the years in his practice were considered too suspect to use in the WPI’s Biobank – which
started anew with new samples. Dr. Lo was able to find XMRV in samples that had been frozen for over a decade. Plus,
the WPI was able to find XMRV in samples from some sort of blood bank, whose sample collection
procedures are apparently
unknown – at least in the detail at which the Blood Working Group is looking at. The upshot is that XMRV
has been found several times in samples which appear to have been collected differently and certainly
not with the kind of care that the BWG is looking at. Can sample collection really be the whole answer?
- That Other Disorder – we’re so understandably focused on CFS that we tend to forget
the other XMRV controversy – prostate cancer. XMRV seems to have a firmer hold on prostate cancer
than ME/CFS at this point. Although the WPI/NCI/Cleveland clinic easily provided the strongest evidence
for XMRV in any disease –
the research community has been focused on PCR and PCR results by independent labs have been less forthcoming
in CFS than prostate cancer. Yet, there’s still no consensus in prostate cancer either.
Take the last four studies; researchers
from the National Cancer Institute looked at 800 (yes, 800) prostate tissue samples using very sensitive
PCR and immunohistochemistry (which Dr.Singh believes may be the most sensitive test of all) and found zero, nothing – not
a single sample was positive – which is what we see in CFS; XMRV is either VERY there or VERY not there.
A Baylor School of Medicine study, on the other hand, found that XMRV was present in 22% of its
144 samples (but questioned its role in prostate cancer). A Netherlands study, broke the ‘all or nothing’ mold by finding XMRV in prostate cancer
but infrequently (4%) of prostate samples. They noted that “that XMRV could not be detected in consecutive tissue sections
of the initial XMRV-positive cases.”; ie, they could find it in one tissue sample from a patient but not in the
next one. They stated XMRV was ‘rarely detected’ and in ‘very low levels’ – and questioned whether it could
play a role in prostate cancer. An earlier Mexican study found XMRV more health
controls than people with prostate cancer (!) (1/55 vs 6/75). Finally, in maybe
the strongest study, a Baylor group used PCR, antibodies
and in situ fluorescence to find XMRV in 27% of people with prostate
cancer. The results of all three methods were in accordance with each other – a
Conclusions – XMRV has never been detected in as a high percentage of
prostate cancer patients (<30%) as in CFS but researchers are finding (or not
finding it) in quite varying amounts (0-27%) and the role it plays in that
disorder is unclear as well. As in ME/CFS most studies have concentrated on
using PCR. The correct methodology for finding XMRV in prostate cancer is still
being investigated. Oddly enough, given the focus on CFS, and most importantly
the blood, we will know far sooner the best way to find XMRV in the blood than
in prostate cancer.
- Nominate the WPI for the American Express To win $200,000 – AE will be
giving 5 charities $200,000 every three months. Who better than the WPI? Check
it out here
http://about.americanexpress.com/news/pr/2010/mp10.aspx and the nomination
form is here:
- A Slim Reid For ME/CFS in Nevada – Sen.
Majority leader Harry Reid is one of our few supporters on Capitol hill and he
is in the fight for his political life. Elections are less than a week away.
Sen. Reid was instrumental in getting funding for the WPI (would we have a WPI
without him?) and knows the Whittemore’s well. Check out a blog by W. Karns
posted on Mindy Kitei’s site going over why supporting Harry Reid is good for
the ME/CFS Community.
- PR Forum Member CrafterKate’s Clever Support XMRV Research Poster
really strikes a nerve as we all look forward to seeing the pieces come together
- Researcher Unlocks Key Factor in XMRV
– Prohealth reported a Univ. of Missouri researcher has unlocked a
key factor in XMRV in replication – something that could pay big dividends as
researchers try to develop treatments for it. Dr. Stefan Sarafianos announced
his lab had unlocked the crystal structure of a protein involved in viral
replication potentially allowing researchers to create a molecule that locks
onto the protein stopping the virus from replicating.
If XMRV is validated in ME/CFS this would appear to clear a path for the development
of designer drugs for the virus. Once again, the mind spins at how fast the research world can work when it wants to.
- XMRV Workshop in Spain – West Meets West – Spain continues to
surprise in the depth of its CFS/FM research efforts. Dr. Montoya from Stanford
will meet with several HIV experts in Spain including Dr. Juli� Blanco and Dr.
Cecilia Cabrera (Biologist�s, HIV experts from Barcelona) and Dr. Vicente
Soriano (HIV expert from Madrid) to discuss XMRV. (Dr. Montoya is well known for
his interest in EBV and ME/CFS and he is currently working with Dr. Lipkin on a
large pathogen study of ME/CFS (including XMRV).
- Amy Dockser Marcus Blogs Again
– with a big yellow ‘X’ adorning her article, our most watchful big media
rep, Amy Dockser Marcus at the Wall Street Journal, blogged about the CFSAC
meeting mentioning the spark XMRV has given both the patient and research
communities, the patient action (yeah!), Dr. Klimas’s call for a national
network of treatment and research centers.
- Dr. LeGrice and Dr. Houghton – both went down the contamination road a ways in
their talks at the CFSAC. (Note, neither did completely. The NCI and Blood
Working Group are looking at other options such as sample preparation
and small differences in protocols.) While the general thrust of their talks was
not anything anyone wanted to hear it bears noting that they are two more
individuals whom XMRV appears to have thrust into the CFS universe….who have
reservations about it now – and yet here they remain...
Houghton, Lasker Award winner, is a CFSAC member and Dr.
LeGrice is now part of the Trans-NIH Working Group (which controls the cash flow for
ME/CFS at the NIH). (He’s one of Dr. Mangan’s big wins as he tries to expand the
reach and the power of the Group). Given their concerns it’s clear that
something other than XMRV has obviously captured their
attention. A talk with Dr. Houghton made it clear that he’s fascinated by the
immunology and by Dr. Lerner’s EBV work and he told me he would work towards
getting more clinical trials for EBV. These are two people whom XMRV has
swept up into ME/CFS’s small orbit and no matter what happens to XMRV – it looks
like they’re staying. We can also throw Ian Lipkin and the other CAA
nominated researchers to the CFSAC committee. These are four year commitments!
Prior to XMRV we couldn’t imagine people like that on the panel. Dr. Vernon told
me she believes XMRV has produced a shift in the research communities awareness
of and interest in ME/CFS.
- Esme Reports: Norway XMRV Study in the ‘Zone’ on XMRV – Much of the research world the WPI wants to
convince won’t be convinced by this because the tests were done at VIPDx but,
look at the consistency of the positive results from Lillestrom Health Clinic in
Norwary; 64% positive -almost right on the WPI’s original figure, and then when you add in the serology results 70-something percent – excellent consistency that is either tracking
XMRV infection in ME/CFS perfectly really or is tracking a contaminant that is devilishly consistent.
Remember Coffins statement about being able to drop mouse DNA in a swimming pool
and being able to find it? If there’s a contaminant one wonders why they don’t
find it in all samples? (It would interesting to compare the protocols of VIP Dx
and Dr. Alter – do they use anything in common? a primer? a reagant? nothing? –
hopefully they are both providing them to the NCI)The most likely outcome of the
consistency of the positive results would seem to be that they are tracking a
virus. This study is helpful but what the WPI really needs is for an independent clinic using an
independent lab to validate its results – not VIP Dx.
Dr. Mette Johnsgaard of The Lillestrom Health Clinic tested 24 patients and 3 healthy controls for XMRV using the culture test and found that 14 were positive. Of the negative tests, 11 were then retested with serology tests and 5 more positive results were found, bringing the total to 19 of 27. One of the positive serology samples was from a healthy control.The Lillestrom Health Clinic has now tested 80 patients and 50 are positive by either culture or serology test � a total of 62%. This is very close to the 67% of positive patient results reported by Mikovits, Lombardi, et al., in Science in Oct. 2009.
The tests were done in cooperation with VIPdx labs in the USA.
Dr. Mikovits to Talk Nov 28th – More information about these results will be given on the 28th of November in Oslo at the XMRV/MLV seminar with Dr. Judy Mikovits. Details of the seminar can been seen here:
http://esme-eu.com/xmrv-mlv-seminar-oslo/category203.html Register by writing to: firstname.lastname@example.org
The Lillestrom Health Clinic is currently cooperating with many international ME experts in order to share knowledge about testing, treatment and research. Dr. Johnsgaard is also cooperating with international experts who specialize in infectious diseases (Borna virus), retrovirology and biotoxic illnesses (Shoemaker), a probable secondary phenomenon in ME.
Larger Study Planned – In November 2010, the clinic will launch a large international research project on Human Gammaretrovirus and ME.
In Aug. 2010, Dr. Johnsgaard was interviewed by NRK (Norwegian National Broadcasting) where she confirmed the two first positive XMRV patients in Norway. With that interview Dr. Johnsgaard opened the public debate about ME and XMRV in the Norwegian medical and political environment. The same day, Norwegian politicians and doctors reacted positively in a follow-up interview on NRK (see links below)
Virusfunn gir nytt h�p for ME-pasienter: http://www.nrk.no/nyheter/norge/1.7257026
Another link with health minister Laila D�v�y – Regjeringen b�r gj�re mer for ME-pasienter : http://www.nrk.no/nyheter/norge/1.7259180
Lillestrom Helseklinikken is situated just outside of Oslo, Norway and specializes in the treatment of ME and other chronic diseases. They have recently begun treating patients from outside of Scandinavia.
- Mindy Kitei’s Blistering Blog
– Mindy Kitei exposed the distance between the
say, your typical HIV researcher who expects nice tidy measurements of viral load – for HIV AND
everything else and CFS patients who are almost being punished for
not having what they could not have at this stage of the game. Its so reminiscent of the
the early days of AIDS when protocol trumped patient suffering and even death. ME/CFS is not
AIDS – people are not dying like flies – but many people are suffering unbelievably and they are disabled and
some people do, and probably are, right now dying.
There are lots of issues in ME/CFS but the basic one is funding and without more
funding we will never know the truth about this disorder, and more importantly
neither will the research community. Are a substantial number of people coming
down with heart disease or dying early? That is something that WOULD touch the
scientific community but it won’t until the
studied rigorously and it hasn’t been. All we have, so far as I know, are two
small and weak studies that contradict each other – and that is exactly the
problem. Researchers don’t care about anecdotal data – it means NOTHING to them
that Joe X or Mary Y died of ME/CFS. Not because they are bad people but because
if they are going to keep being researchers they can only accept data from rigorous, well designed studies and when a
multi-dimensional disease is only getting 4 million or so dollars a year in
funding – you’re NOT going to get those studies. If we want the Canadian
Criteria to be accepted we need studies showing
that that is a better definition…but you can’t get studies like that if
you’re getting peanuts every year.
Mindy points the finger at
the CFSAC but there’s also us – a community of 200,000 people (reportedly!) in
the US that didn’t fill
up the speaking slots, (telephone or otherwise) at last weeks CFSAC meeting and
that left a small conference room that is within traveling distance
of millions of people half or more empty. How many hundred or 1,000 people with ME/CFS live in Washington
alone? (Somehow sick Mary Schweitzer, again, dragged herself all the way from Reno, Nevada.
Mary, whether she is wheelchair bound or not is always there :)) Last year CFSAC nominations came from
groups all over the US; this year the only one I heard of was from the CFIDS Association.
As a community our efforts are still disorganized and feeble. Hopefully the Time
for Action campaign will provide a opening many people will step into. We do
have the power – if we realize it – to make a huge difference. Mindy’s blog is about THEM but it’s
also about US – the
need for us to stop waiting for someone else to do it (aka the CFSAC) and embrace the opportunity, as many did, before us in the Time for
Action campaign and to continue acting.
- XMRV at the Tipping Point: A Tale of Two Conferences
– check out my take
on the last couple of weeks findings.
- Sue at LiveWithCFS Blog – updates her NJ Conference Summary
– 80% of Dr. Cheney’s patients were postive for XMRV. Why is that such good news? Because it
we expect that the percent of XMRV positives will go up the more CFS is rigorously defined. His study won’t have much sway since it used VIP Dx but since contaminants
don’t care how rigorously anyone is
defined this is another nice check on the contamination talk. Fifty percent of the family members of people with XMRV
were also positive (ouch!!!). The UK study provided another nice check; 50% of patients were positive by PCR and that figure
went up to 80% using more methods and there was that low postive rate in the healthy controls again.
Dr. Mikovits she has a drawer full of studies no one will publish. This is undoubtedly the way it will be
until XMRV’s fate is clarified – at which point, the WPI, hopefully is redeemed (in a very big way) and
publications start clamoring for publications from the little Institute that indeed rocked the world.
(But why not the UK study???)
Sue reported “Dr. Mikovitz also said that some of the people who’ve been
suggesting contamination are people who were involved with the original studies and who saw all of
the original data, including those which proved contamination was impossible” – the inference being that
some people just don’t want this finding to come out. I would guess, however, that it just reflects the
uncertainty in the scientific community (and the Weiss paper that just came out); on the one hand you have
“the best first study’ you could think of, followed by a raft of mostly
negative studies. My guess is that the
scientific community is more than a little puzzled how to put these two results together. The fact that the Blood Working
Group and the NCI are looking at every detail, from blood storage to small methodological details that usually
aren’t even printed suggests they are more confused than anything.
Slipping Into Conspiracy Theory Mode – there was also this “The prevailing
theory seems to be this: if the CDC confirms that XMRV, a new, dangerous,
and transmissible retrovirus, is present in people with CFS (and the CDC
has estimated the number of adults in the US with CFS to be 4 million),
then they have a huge public health crisis on their hands.”
Boy do I not
buy this. For one, this is way bigger than the CDC – we have multiple federal and other
groups working on XMRV. For two, I don’t think the government is in the business of
covering up pathogens – call me naive, I just don’t – particularly when well known researchers
from several different branches of the govt are involved. Coverups don’t
work very well once they spread beyond a small group of people. Nor would the
hire an ace pathogen detective to lead the search if it was interested in
covering up anything. For three – any attempt to coverup this pathogen is doomed
to fail because other, good researchers are involved – the truth is going to
come out. XMRV just happens to be a tough nut to crack
- Cracking That Nut – Dr. LeGrice, if I didn’t report it before, told me he
thought the contamination (and I suppose, blood storage issues) will be resolved
within 3 weeks. The prognosticators have all been wrong thus far on time- so
let’s give him a bit more time; say a month from now – according to Dr. LeGrice,
we should know.
- Dr. Mikovits Talks –
- Cooperative Diagnostics Study Gets Expected Results –
The Cooperative Diagnostics Lab jumped on XMRV early and their long-rumored study
has finally surfaced but it was on autism not CFS. (Reports are that no XMRV was found in their CFS patients). Using CDC assays and the
prostate cancer XMRV clone they reported zero XMRV from PCR and antibody tests to autistic children born to parents with CFS, other autistic children and people with fibromyalgia. While this
study did nothing to strengthen the XMRV/CFS connection the ability of CD to come up with that many CFS parents with autistic children was an
eye-opener for me.
the Patient Advocate has been busy. He was at the
Research section of the CFSAC meeting, then it was over to New Jersey for the
New Jersey conference. If you’ve seen Dr.
Mikovits talk you know that when she talks she can really talk – she’s almost
like a force of nature when she gets going…and she really talked at this
You’ll have to read Chris’s blog
to get the complete picture but some key points stuck out.
Dr. Sandra Ruscetti, a co-author of the original Science paper, has
generally been in the background but she is a key, key figure because of her long experience with the murine
leukemia viruses (MLV’s)- of which XMRV is one. The point is that she’s tangled with these
viruses (and the contamination problems they pose) for a long time and Dr. Mikovits
reportedly referred several times to the key role
she played in isolating the virus.
“Sequence Diversity is Our Friend” – Dr LeGrice referred to the
genetic homogeneity of the virus in the Science paper – a red flag because contaminants don’t mutate but viruses do
but this has always been a weak point because it was founded, as I remember, on
the sequencing of only two and half strains. Dr. Mikovits pointed out that as XMRV is studied more
the WPI is finding more and more sequence variation – a very good sign.
Reservoirs – XMRV is found in very low amounts in the cells studied thus far – perhaps too low to cause
alot of damage (although there is some disagreement here)- so it would behoove researchers to find a tissue it is
replicating in. Apparently Dr. Mikovits has some ideas (or results) about that but what exactly they
we didn’t get. She at least has enough information to speculate on them.
“Sample processing is everything” – The Blood Working Group is going
back to the drawing board and looking at very basic aspects of sample processing in their
search to explain the disparate results. At the XMRV Workshop Dr. Mikovits
intimated there was some big news here. Dr. LeGrice wasn’t willing to go so far
in his talk but now our PA reports that Dr. Mikovits stated ‘sample processing is everything’. Hopefully so;
several candidates to explain the results have popped up over time; there was culturing
(or the lack of it),and there was APOBEC3 editing and/or the use of the prostate clone. Perhaps they all play a role in the
funky results gotten thus far.
The X Variant and P-Variants are not Variants at all But Separate Species -Alter/Lo
are reportedly fleshing out the full genetic sequences of their ‘pMLV she’s” but the WPI has
their samples as well (hundreds of them reportedly) and they have apparently fleshed out
their sequences as well found that CFS patients contain a bevy of closely related
but different viruses – not variants – which is what both LeGrice and Coffin
The evidence for several different types of MLV’s
in CFS is – the pMLV’s from Alter and Hansen study, XMRV from the WPI study and, now confirmation of the pMLV’s from the WPI. Presumably the
WPI found the pMLV’s in the original study but because they only sequenced 2 1/2 viruses – which looked like XMRV – the pMLV’s
did not make it into the original paper. Now that they’ve sequenced more of the several hundred isolates they have – the pMLV’s are showing
up; they were there from the beginning but were hidden from view.
But why did Alter/Lo only pick up the pMLV’s in their samples?
We don’t know but Dr. Mikovits reported that when Dr. Ruscetti cultured Alter’s samples he found XMRV as well – which, of course, is
great news The WPI/NCI findings, if they hold up, will destroy the attempt to present the Alter/Hansen studies as ‘unrelated’ to the WPI’s XMRV finding.
XMRV and its variants are not mouse virus’s – It will be interesting learning what this means; if not a mouse then what,
a uniquely human virus?
There’s much more than that. It was clearly a whirlwind presentation and one wonders if only Dr. Mikovits could
have gotten so much information in in under an hour.
The dichotomy between the two XMRV ‘camps’
at the moment is astonishing. Just a few days after
Dr. LeGrice warned about the ‘very real’ possibility of contamination Dr. Mikovits blew the wheels off the
XMRV story with her report of how the WPI and Dr. Ruscetti continue to deepen their understanding of this virus. Dr. Mikovits was
clearly very confident at the New Jersey Conference, and that in itself is good
news for XMRV.
Oct 15th –
- So How Much Does it Cost to REALLY Study XMRV? – well, it costs alot of money.
At the IACFS/ME Conference we found out that Ian Lipkin’s multicenter XMRV
study for CFS is going to set the NIH back a whopping 1.3 million dollars. We haven’t seen a million dollar study
for CFS since the Centers For Disease Control started their Patient Registry project….(ba
da bum….). So far the NIH has awarded
three grants to study CFS and XMRV for a grand total of about $2,000,000; the Lipkin is easily the largest and the others include Dr.
Hansen’s $270,000 look at Dr. Bell’s patients and Dr. Singh’s $312,000 look at Dr. Bateman’s patients.
One wonders what the total cost of the effort at this point are. The great thing
about these studies is that the wealth of data these experienced doctor’s can provide. Thus far Dr. Peterson, Dr. Levine,
Dr. Cheney, Dr. Klimas, Dr. Lapp and Dr. Bateman in the US (and I’m sure I’ve missed some)
have contributed CFS patients for XMRV studies.
Oct 14th –
- XMRV Redux at the CFSAC Meeting – Still smarting from not asking Dr. LeGrice the
question I asked Dr. Houghton. Dr. Houghton, I found out, is, believe it or not a Lasker award winner
for discovering hepatitis C, but he is not a retrovirologist and retroviruses are very different from viruses.
When I popped the antibody question he said well, the antibodies could be cross-reacting with another virus
which in itself would be interesting – what virus could that be? Another MLV?
I said but consider what would have to
happen for both the PCR AND the antibody test to be wrong. First you have a strange and difficult to pin
down case of contamination. Then ME/CFS patients (but not the healthy controls) will
have to just happen to be harboring another virus that the antibody
test just happens to pick up. (???) The statistical probability that both things
went wrong (in just the right way) have to be extremely low. Dr. Houghton agreed that that was an issue. He
also made clear that he
thought the Science paper was an extroardinarily well done paper.
Dr. Houghton also wanted to be clear that a) he was providing his personal opinion, b) he is not a
retrovirologist and c) it was the Weiss paper that really turned him around. By the
way, he was very impressed by the
EBV findings presented at the meeting; he said CFS looks like a viral disease to him
and he’s going to work hard to try and get something done with EBV.
That “Zone of Chaos” – How much are researchers befuddled? The NCI is developing a website where
they are asking researchers to make the tiniest details of their protocols public so that they can examine and see
if something very small –
and, heretofore unthought of – might be causing the disparate results. The fact they are interested in doing this
can only be a reflection of the strength of WPI’s original work. There’s the PCR
work, the antibody work, growing the virus, showing that cell free media from
the patients blood could infect other cells….these are all interlocking pieces of the
puzzle – each of which strengthens the other; its difficult to break that
chain…….there is clearly no easy answer to the differing results.
The CFIDS Association – Glaxo-Smith Kline XMRV study – I asked Kim McCleary how the
GSK XMRV study was going and when the results
would be back. She said it was in the hands of GSK. Was culturing being done? Yes, she said the investigators had been in
touch with the Dr. Mikovits in order to get her exact protocols and that they were doing
extensive testing. The
study is double-blinded – so they won’t know anything until they break the codes and
then all will be revealed but she didn’t know when. I asked if the study
would be published and she said publishing is a requirement for using BioBank samples.
The Klimas Study – Dr. Klimas has had her CFS samples at four labs, if I remember correctly, since February. One of
them is in a Yale lab lead by a co-worker of Dr. Singhs. No funding has been provided so they
are doing the analyses slowly. The announcement that an edition of Retrovirology early next year (I think) will be
devoted to XMRV, will hopefully, Dr. Klimas said, speed up the process. This should be a particularly valuable study because of
all the other data (including alot of immune data) Dr. Klimas has collected on these patients.
That Negative Chinese study – with regard to the Chinese study Kim McCleary said – people in the US have
enough trouble defining and diagnosing CFS here – which makes it very difficult to assess anything that
comes out of China, which does not have a background in CFS research.
- XMRV’s Tough Week – at the CFSAC Meeting Dr. Stuart LeGrice presented an overview of the
Workshop but the gist of his presentation was clear; he believes there is a good chance
the positive XMRV results are due to contamination. Citing how incredibly PCR’s have become at
picking up the smallest amounts of DNA (eg Dr. Coffin’s analogy swimming pool analogy) and
how ubiquitous mouse DNA is in medical research environments he laid out a case for some sort of
unforseen contamination. The disparate results have clearly got the researchers at the Blood Working Group
flummoxed and they are looking, he said, at aspects of PCR and sample testing they’ve never looked at in
Dr. LeGrice’s guess, at this point, would tend towards contamination at some part of the
‘food chain’ but he is not tied that and cited other possibilities the Blood
Working Group is examining including how long the blood is stored, what test
tubes it is stored in, how long before it sits out before it is frozen –
basically they’re looking at every stage of the process. At the XMRV Int.
Workshop Dr. Mikovits intimated they had found a key factor in sample
preparation that could explain the disparate results; if Dr. LeGrice knew
about that he wasn’t saying but it obviously remains a real possibility. The only good news from Dr. LeGrice
on the contamination front was that if mouse DNA is involved they should know and soon – within 3 weeks, he said,
he thought the contamination question will be laid to rest one way or the other.
Dr. Houghton – He was followed by Dr. Houghton, a hepatitis C researcher, and CFSAC panel member who also leaned
heavily on the possibility of the cotamination stating that the events of the last couple of weeks had
dampened his enthusiasm for XMRV. He cited how easily it was to reproduce the result of the hepatitis
c when it was first found. On the other side, though, we have Dr. Singh who’s
worked with mouse retroviruses for 10 years and
with XMRV itself for four who told me she was not surprised at the trouble researchers were having
clarifying XMRV and who felt contamination was not a possibility. We also have Sandra Ruscetti, an important
figure in murine retrovirus research for decades who also presumably knows how to handle murine retroviruses – so we shall
Unfortunately my mind went blank after LeGrice’s presentation and I forgot to ask the key antibody
question – how can you have antibodies to a contaminant? He obviously would
have an answer to such a simple question but it would have been good to hear it. I will try to corner Dr. Houghton today. More on
news on XMRV from the CFSAC meeting (it’s not all bad) when a summary comes out.
Three More (Negative) Studies – Meanwhile three more negative studies came out; a UK/Swiss study involving Dr. McClure
found no XMRV in several hundred patients with HIV or hepatitis C, the Mass Felsenstein study looking
for it in
CFS, HIV, rheumatoid arthritis and organ transplant patents and a Chinese study looking
in CFS patients. The Felsenstein
study was painful given the high hopes for it.
- Now They’ve Done It! – the long rumored ban on blood donations in the UK was finally announced not because the
patients are viral but because they are ill and like other patients with -remitting-relapsing conditions like MS, it just doesn’t
pay to risk a relapse. It must have sounded odd to UK ME/CFS ears to have the goverment lump them in with multiple sclerosis
– a ‘real’ disorder deserving of real research in the UK’s books but there it was. This time the BBC actually tried to cover
both sides of story, citing the retrovirus connection some (deluded :)) patient groups think might also play a
role in the govts decision.
- Who is Stuart LeGrice and Why is he Speaking at the CFSAC Meeting? – Dr. LeGrice will author the XMRV presentation at the CFSAC tommorrow.
We haven’t heard alot about him. His name did poke up early in the discussion when he noted how many drugs might
available for XMRV. The director of the National Cancer Institute’s Center of Excellence in HIV/AIDS and Cancer Virology, he
has, as one suspect, quite a resume having co-authored over 155 papers, many of them on HIV/AIDS. He’s another example of the kind of top-flight researcher XMRV has attracted. Other than professional interest his direct
connection to the virus is unclear.
- Dr. Mikovits is on the Move – Dr. Mikovits just spoke at UCLA and will be darting up to Oslo, Norway on
Nov 28th to give a talk on “XMRV and other MLV’s in Chronic Fatigue Syndrome”, the title suggesting, of course, that the
pMLV sequences found in ME/CFS actually belong to different MLV’s and not to variants of XMRV.
(Thanks to Anne for the tip).
Lewellyn King Talks – White House Chronicler Lewellyn King sides with CFS. You don’t
hear this kind of perceptive talk much. Check this out “Yet there is a vast archipelago of diseases as cruel in their impact, horrible to bear and crying out for research that is not sporadic, underfunded or, through ignorance, misdirected.”
The man is speaking the truth to power. And then there’s this
One such is Chronic Fatigue Syndrome (CFS), a name so gentle that it belies
the ghastliness of this affliction. Sufferers accuse the U.S. government,
abetted by other governments, of choosing this name over
the older and more commanding name, myalgic encephalomyelitis.
Plus there was a roundtable Mr King led which
on PBS that blogger Heida Bauer thought went quite well. Check out her blog for news of the PBS version of CFS and XMRV.
Keep talking Mr. King.
- ACT UP for CFS and XMRV! –
Peggy Munson argues it’s time to ACT UP for CFS in her latest
blog: the Best Offense is a Good Offense – there’s no denying Peggy is onto something
powerful when she suggests that above all it would help if people with ME/CFS made
some more noise. My brother is a lobbyist and he told me that the squeaky wheel does definitely get the most
grease. It’s not as easy for CFS as it was for AIDS in the 1980’s. Gay people often
lived in close contact -making it easier for them to organize when HIV/AIDS hit
while many people with ME/CFS rarely have occasion to physically meet someone
with their disease but we do have the internet now. I don’t agree that attempts to use the
‘inside voice’ have reinforced the power of those keeping us down – I think all attempts
to advocate do
just the opposite but there is no doubt that we have barely scratched the surface of advocacy – something
Peggy’s blog vividly demonstrates.
What is Next For XMRV? – Check out some of the studies we may be looking
forward to seeing over the next couple of months.
- heck out the Newly Updated (and Color-Coded) XMRV
- MLV’s, AIDS, ME/CFS and Alcohol Intolerance
– Nasta778 on the PR Forums posted a very interesting abstract. What do researchers do to induce an AIDs’like
condition in mice? They don’t give them HIV….they infect them with MLV’s (!) because MLV’s play havoc with their
immune systems causing them to have an ‘immune deficiency syndrome’
infections. The paper reported:
The similarities between murine AIDS and human AIDS are striking, with similar changes in immune functions, T-cell differentiation,
cytokine production, disease resistance and oxidative stress�”
Of course mice are not humans but it is an interesting correlation…MLV’s =
AIDS in mice, ME/CFS in humans????
When they fed the MLV infected mice alcohol a strange pattern of protein expression
involving one mitochondrial protein emerged which appeared to exacerbate the effects of the original infection. The abstract ends “These results suggest that chronic alcohol consumption may exacerbate the effects of viral infection on the heart
by lowering the stress response leading to de-protection and further cytotoxic effects.”
One wonders what effects alcohol consumption
in alcohol intolerant people such as people with ME/CFS has? Does this finding say
something about the problems with alcohol intolerance in ME/CFS? Could small
amounts of alcohol be disrupting the stress response, mess with the mitochondria and
result in increased oxidative stress? The alcohol conundrum in ME/CFS to my
knowledge has never been addressed anywhere….
How common is alcohol intolerance in ME/CFS? Let’s find out – take the
Alcohol Tolerance Poll!
Stays in the Hunt– Kate Bishop, a UK researcher, was part of the Groom-Kerr team which did
not find XMRV but she also discovered the APOBEC3 editing that was a revelation to Dr. Mikovits and which Dr. Mikovits believes
could explain some of the negative study results.
Voner in the PR
Forums reported that she is starting up a big project to look at various factors including XMRV prevalence
on the general population and ‘in patient groups of particular interest’ – which, one would assume, does not include ME/CFS – unless
she has developed new techniques. She does report that besides the PCR and serology tests her lab has developed she is
developing ELISA tests for large scale screening and culture tests…note that she is developing CULTURE TESTS….(how
could she not run a few of her blood samples through them????)
She’s also looking at how XMRV infects different
cells under a variety of condition, at hormonal and IFN-10’s effects on it’s activity and more. There’s alot going on in this study – it’s a big effort and indicates that,
at least with this UK researcher, interest in XMRV is alive and well.
Big Pharma Waits….On XMRV – a question to Dr. Light at the CFIDS Association Research webinar about the diagnositic capability of his exciting work on increased muscle and other receptor increases in ME/CFS shed some light on how Big Pharma works. Dr. Light’s work suggests people with ME/CFS have a distinct receptor signature – basically a biomarker, and therefore possibly a diagnostic tool (finally) for ME/CFS. It’s definitely exciting stuff. He reported that Pharamceutical companies were interested in developing it until XMRV showed up with it’s promise of a cheaper, easier biomarker. One thing at a time for Pharma…
- Hillary Johnson on the XMRV Workshop –
a lively, hard-hitting and sometimes humorous blog from Hillary Johnson. She
talks rather poignantly about sitting with Paul Cheney 25 years ago in Incline
Village and now at the Workshop and the progress has been made in the last year.
Dr. Cheney discusses XMRV and Anti-retroviral treatments – in his
Check out a teaser here. Subscription required, of course, for the entire
Aktion Time! – Email, phone or fax NIH officials for more funding into XMRV
and CFS on the cusp of the CFSAC Meeting in 10 days.
Check out Mindy Kitei’s interview with the
- Dr. Mikovits Talks – at the New Jersey CFS
Conference on Oct 17th.
- XMRV Article
Shows Up in Hemophilia Site – the only question is what took it so long? If
XMRV is in the blood supply and the blood supply has not been screened for it
then hemophiliacs would. just as they did with HIV/AIDS, presumably take a big
hit. No one has shown that yet but if I had to get transfusions with some
regularity news that a new RETROVIRUS, of all things, might be in the blood,
suppose would catch get my attention.
- XMRV Positive Survey Posts
Results – the XMRV positive survey has found that of the 55 respondents 60%
had acute onset and 37%, interestingly enough, had gradual onset (interesting!)
A full third had mononucleosis and believed it contributed to the onset of their
disease. The most common age of onset was easily from 30-39. With some nice
colorful graphs – nice job! Functionality would be interesting to determine – is
there a range of illness severity or were the XMRV positive patients really ill?
- Brits and Yanks Square Off over XMRV
– Dr. Erlwein, Dr. McClure and the rest of the Imperial College
retrovirology team (plus Dr. John Martin after all these years!) attempted to pin the Alter/Lo tean in the US down with some tough questions in
PNAS’s Journal Letter section. Alter/Lo had to respond and they did. Were they nailed to the wall? Or did they
knock the Brits questions out of the park? Check it out in
Batter Up! The XMLV/MLV debate
- A Rumor of Viruses
– Thirteen years ago John Weiss was burned by a viral discovery that, years
later, turned out not to be one. The author of ‘Rumor Viruses’ he’s made it his
job to warn the research world of the perils of viral discovery. Now in this
PubMedCentral article he’s turned his attention to XMRV.
He makes the point that XMLV’s (Xenotropic murine leukemia viruses)- which are
distinct from, but closely related to XMRV’s – are commonly found in labs that
have done cancer research and may be widespread in laboratory reagents. He notes
that the Hot Taq polymerase enzyme has mouse antibodies and can carry XMLV’s
(Check out the above article for Alter/Lo’s response to the Taq question).
Except for one other type of virus murine leukemia viruses are the most
problematic because of their prevalence in the medical research worldp ie it’s
easy to contaminate a sample with them.
The most intriguing part of Weiss’s essay concerns his own
viral discovery that turned out not to be one. In that instance, as well, the putative virus was found in more
sick patients than healthy controls – seemingly a clear sign that contamination
had not occurred. As to how or why the
occur, Weiss was never able to tell – the only idea he could come up with was that the ill patient samples
had been handled more than the healthy control samples and that somehow allowed the contaminant entry.
His story pointed out the cautionary tale that even labs that seem to do
everything right can fail.
notes that “If the healthy samples had come from strictly derived case-control collections in which the control vials
were handled in exactly the same manner, for the same time and with the same frequency as the vials containing the clinical specimens (which has not been done for CFS), we
might not have observed the bias towards detection in cases above controls.”
Reading Dr. Weisses recipe for success, however, does make one glad for the
Singh study (and probably others) which are doing exactly as he recommends.
Another point he brings up is the apparent ease with which both the WPI group
and Alter/Lo group found the viruses. Both were able to pick it up using a
single round of PCR while other groups were unable to find any trace of it (or
them) after two rounds of PCR – a good point that Alter/Lo responded to but
which has yet to receive a definitive answer.
Dr. Weiss does bring up some good points but I found his paper to be
surprisingly light; more an essay than a probing analysis of a problematic
finding. There was no discussion of how effective the efforts of the WPI, NCI
and now Alter/Lo labs to account for the presence of a possible contaminant
were. There was no discussion about geographical differences in sequences or the
possibilities of recombination or different primer sets. In the end Weiss took a
rather anecdotal approach to warn the research world about a finding he thinks
is spurious; a not very convincing combination at all and one which I guess will
do little to advance his cause. Certainly the ‘opposition’ can be more rigorous
in their appraisal of XMRV.
- Patients on Retrovirals Talk…to Mindy Kitei – Blogger Mindy Kitei would like to talk to
ME/CFS patients who have tried (or are trying) antiretrovirals on or off the record. Email: email@example.com
- Ali Deckoff-Jones Goes Back to School – Dr. Deckoff-Jones daughter is back in school. She may not be kicking up her heels all the time
but how much progress she’s made readily becomes evident in the story she tells of her
last attempt at school; not a pretty one that was
filled, as has so often happened, with arrogant school officials telling her to
‘just cowboyup girl!”. (That didn’t go over well. Doesn’t everyone have at least
one memory like this? I still remember my consult with my University MD decades
ago…) She reports that CFS ‘stole her voice’ before and now she has it
back- and she’s talking (and she’s a good writer, as well :)).
- Dr. Deckoff’s Blog “My Opinion” is Very Intriguing
– Look at any organ system she said – you’ll find problems, but that does not mean that that particular organ
system is ‘it’ in ME/CFS. Having been athletic for years
after presenting with
diastolic dysfunction (which has actually improved over time) she is no believer
in the importance of diastolic heart failure, for instance. (Unfortunately no
attempt has been made to fashion together a coherent theory regarding diastolic
dysfunction and plop it into the
medical journal dedicated to theory. A mother of a daughter with ME/CFS got her H2S theory published last
year). She notes that the ‘heart failure’ possibly present in ME?CFS is definitively not the heart failure
leads to complete heart failure and death, usuually within a few years (something Dr. Cheney
goes to some pains now to point out. He always did
point it out – but the phrase ‘CFS Patients are in Heart Failure’ seemed to
easily drown out that fact at the time.)
Dr. Deckoff would suggest that all these organ system abnormalities are probably
due to viruses (something Dr. Cheney, in all fairness, appears to agree to).
Then she goes onto explore the pluses and minuses of anti-retroviral therapy and
of XMRV itself. The fact that some people with XMRV are completely healthy means
it’s going to be XMRV plus that does the deal in ME/CFS patients; XMRV plus a a genetic abnormality or XMRV plus another virus or
plus ???? The gist is that while we do have some data we are in the early phases
of learning what works and what doesn’t. Nevertheless Dr. Deckoff is
increasingly clear that retroviruses are ‘it’ or, at least a big part of ‘it’ –
at least in her and her daughter’s case and who can blame her? Her daughter is
back in school and she is beginning to think of
returning to practice.
- The Future of XMRV Testing: HIV and XMRV
– a look at the ‘options’ available for HIV testing suggests what the future
of XMRV testing will be like.
Check out what happens in HIV. First PCR tests aren’t even a option for HIV
because they are expensive, difficult to administer and more difficult to
interpret relative to other testing options.
and immunoassays are the ticket in HIV these days.
Because there is a small
chance of a false positive antibody test (even now) a positive HIV test needs to be
followed up with another test and you generally have your choice of four; a
Western Blot Assay – which is accurate unless you happen to have another viral
infection going on (in which case it’s not), an immunofluorescence assay, a line
immunoassay or if you can’t get those, a second ELISA test (using a different brand of test.) Having two
positive tests means you are definitively positive for HIV.
Not surprisingly given XMRV has just caught the research worlds attention
recently, we are far from that level of sophistication. We have the PCR test
and the antibody test but since a positive result from either means that you are
‘positive’ there is no ‘check test’ yet. At some point there will be
one – probably some sort of immunassay combined with the standard antibody test.
(Note that with HIV the number of false positives is, of course, very small
(0.2%) – we’re not talking huge numbers of people that would become wrongly
informed they have HIV if they just took one test.)
- Of Mice and Men: The CFIDS Association Report on XMRV Workshop
is out. The CAA issued a pretty comprehensive report on the
XMRV Workshop complete with images.
Living with CFS Blogger Talks With Dr. McClure – ‘Living with CFS’ basically
got Dr. McClure to get down to the nitty gritty about XMRV in a series of
emails. Dr. McClure believes the WPI’s results and presumably Dr Alter’s results
(and Dr. Hansen’s results? and the UK Mikovits study results?) are probably due
to contamination and were confounded by the fact that blinding/randomization was
not done and that not all the samples were treated ‘in the same way and at the
same time’. Of course she has her points – she is a published retrovirologist –
and we shall see. Dr. Singh is in the middle of her study which is designed to
answer all of Dr. McClures concerns and, of course, the DHHS and NIH studies
will as well.
Dr. McClure is making some big claims here – she’s out in front of
most researchers in her certainty about the situation – and we’ll see if she’s
right and if Dr. Mikovits, the Ruscetti’s, Dr. Silverman, Dr. Alter and Dr. Lo and Dr.
Hansen (and even Dr. Singh – who said she saw no chance of contamination) are
Most researchers are still sitting on the fence. My guess is
that the situation will be over, one way or another, when Dr. Coffin starts
leaning one way or another. For now he’s on the fence; Dr. McClure, on the other
hand, has maybe one
toe on the fence. We shall see if she ends up looking prescient or if she ends
up looking like somebody who spoke too much too publically too soon.
Dr. Mikovits Lectures at Center for AIDS Research at UCLA – We’ve
heard just a bit about how ‘promiscuous’ the MLV viruses are; how they like to
recombine with each other. At one point Dr. Mikovits suggested more than one
virus or variant may be needed for them to survive in the body and Dr. S.
Ruscetti is reportedly looking at this now. Dr. Mikovits will be digging into
some cutting edge research on her talk “MLV related viruses in neuroimmune
disease and cancer: Is XMRV or PMRV the pathogenic variant or does it take two
to tango?� in her talk on Oct. 8th. Thanks to Berthe for digging this up.
Dr. De Meirleir Talks – Lot’s of stuff in Berthe’s report on Dr. De
Meirleirs talk on XMRV. Dr. DeMeirleir was definitely ready to talk and he
spilled the beans on the results of a number of ongoing studies. He said XMRV
has been found in ten diseases (!) which could be good or bad news depending on
which diseases it was found in. (NEID’s, cancer, autoimmune and neurological
disorders – good; just about everything else bad.) The Alter/Lo study is being
replicated in Europe; so far about 50% are testing positive for XMRV. Another
study will show XMRV is transmitted sexually but he is not supposed to be
talking about it (shhhhhhh……). He does not appear to be that excited about
anti-retrovirals. The Blomberg study patients came from him.
- MLV’s Showed up in ME/CFS in 1994? –
Mindy Kitei found an intriguing reference to a report by Diack of murine
leukemia retrovirus like particles isolated in a third of ME/CFS patients. The
authors noted how preliminary the finding was and the ‘considerable work’ needed
to clarify it – which apparently was never done.
XMRV Shows Up in Autistic Child and Mother – in a long and interesting blog
Kent Heckenlively reports that his wife, his autistic daughter and his
mother-in-law have tested positive for XMRV. His wife, interestingly enough, has
been showing showing increasing cognitive problems and his mother-in-law has
celiac sprue. He believes XMRV’s integration sites into cellular genomes fits
well with the methylation and mitochondrial problems that may be occurring in
autism. He also questions whether XMRV infection in the blood vessels of the
brain could be affecting both CFS and autism patients. He notes that the
treatments being discussed on the Phoenix Rising Forums mirror those being
discussed on autism sites.
- Dr. McClure Talks
– At a panel for the American Society of Microbiology Dr. McClure stated she was
starting to work on prostate cancer patients with XMRV when she was approached
to test CFS patients even though she had no experience with CFS. Since her PCR
was ready she agreed to do it. She stated that the patients whose samples she
tested had the been the focus of 150 papers (!???). She took a hard line against
Alter/Lo’s contention that their paper confirmed or validated the WPI’s findings
-stating that it didn’t -and then she noted that the pMLV’s found were more were
more closely related to the dreaded endogenous retroviruses than to XMRV. She
stated the genetic sequences she used in her PCR should have picked up the pMLV’s
that the Alter group found.
She does not believe the disparity in results could be due to patient selection.
She got a little snarky when she seemed to
indirectly suggest Dr. Mikovits does not know basic virology when she said Dr. Mikovits wants us to isolate the virus but,
of course, we can’t isolate the virus until we find it.
She noted that
her group was criticized for not using the same primers as the WPI and that they
went back and subsequently used the same primers as the WPI and still didn’t
find anything – which is something we have not heard. She also stated that that
her positive control was Bob Silverman’s prostate cancer sample – which Dr.
Mikovits believes is problematic. While at times saying the right things her
overall stance to XMRV is emphatically that it’s not there; she continually
emphasizes negative findings while giving little heed to questions that have
been raised why those findings might
be wrong. She is a long way from Dr. Singh’s cautionary warnings about the early
stages of research or even Dr. Coffin’s ‘zone of chaos’; in her mind the issue
appears to be settled.
She did note that the interest in the virus was
extroardinary and that the Director of NIH was present in several sessions of the Workshop. (Dr. Vernon said
she was astonished to see him sit through 75% of the Workshop – something she had never seen before). Dr McClure stated that
her opinion really didn’t matter (which is true, although she does keep repeating it
:)) and that it will
ALL be sorted out in a few
- And Talks – Dr. McClure appears to be enjoying her time in the limelight;
besides her initial study she has done two videotaped chats this week, she has
penned several editorials and she has been interviewed several times; for
someone with no connections to CFS she has become quite connected very quickly. Dr.
Racaniello caught up with her at a huge meeting (10,000) and they had a rather
long and quite involved talk. Whether she’s right or not she is clearly well
versed in the field.
Although she stated she has doubts she is planning on
replicating the culture techniques recommended by the WPI using samples provided
by them. (This appeared to work for Dr. Hansen). She believes XMRV is real in
prostate cancer and not in ME/CFS, at least at this point. Dr. Racaniello
pointed out that only the Science paper by the WPI had a positive control to
test off of – something she seemed to agree was important. (Dr. McClure lauded the CDC paper
“it was the one we were all waiting for” thiswhile Dr. Racaniello largely
dismissed it because it did not have a positive control). Interestingly, she has
never met Dr. Wessely! (It was his samples she tested.)
Dr McClure noted that
MLV’s have never been found in humans before while Dr. Racaniello noted that if you drop human cells, if I got this right,
into mice tissues they become infected with gammaretroviruses (the potential is
clearly there). She felt it was rather strange for two separate viruses
(XMRV/MLV’s) to show up in two groups of ME/CFS patients and clearly still
believes contamination could be a factor. They both agreed
that XMRV/MLV’s could be present in the human population but only show up in
people who were ill. The interview takes place about 45 minutes into the tape.
- XMRV International Workshop Abstracts Part II:
German Researcher Draws Blanks Again – Norbert Bannert is not having an
easy time with XMRV. First he tried to find it in prostate cancer and failed and now he’s to find it
in ME/CFS and failed. Unlike other researchers he activated the PBMC’s he sampled and then cultured them
in order to boost the viral presence but he used a different process than the WPI and Dr. Hansen did.
Then he tried to transfer the virus to the LnCap cells the WPI does use in at least some samples but to no avail.He did show, though,
that XMRV is infectious; that is he was able to produce the virus from a cell line and showed that it
could infect cells. His particular population – a small group of 39 CFS patients –
was negative, as were his healthy controls and a group of MS patients. if
Swedish Study Comes Up Empty – Dr. Blomberg and his ‘Swedish XMRV Study Group’ – used quantitative PCR – the same type of
PCR Dr. Singh favors, to look for XMRV. Dr. Blomberg used the same LnCap cells the WPI recommends to culture the virus for five days
for the same period of time
the WPI recommends. Blomberg found
no XMRV in 50 people with ME/CFS, 400 prostate cancer samples or 200 controls using what he called his ‘novel’ PCR methods.
He did get a few weakly positive (or ‘uncertain’) samples from ME/CFS patients. We can see from both these studies and the Mikovits and
Hansen studies that as time goes on studies are getting more complex and are starting to hue more towards using the
WPI’s techniques. Dr. Singh is currently engaged in an XMRV study in Salt Lake City which is using LnCap cells as well.
XMRV Blood Working Group is Halfway There – Key Problem Identified? – Phase II of the project, which compared different labs ability to
find XMRV in WPI identified positive patients is complete! One thing they looked was whether the 2-4 day delay in
processing that is common in many labs affects a labs ability to find the virus. Dr. Mikovits’
stated that blood preparation techniques are important and it brings to mind Dr. Singh’s
painstaking attention to this factor in her study. (What an astonishing finding
that would be if it was something as simple as blood storage all along….) In Phase III they will determine the best assay using blinded tests
and in phase IV they will look at 300 samples from the Western United States. They will be done by the end of the year.
Finding XMRV’s Tissue Reservoir – Dr. Ruscetti stated that the results from the Science paper suggest that XMRV is not very
active in T and B cells in the peripheral blood – the main players in the adaptive immune response.
His study looked further into the immune system and found that it can infect two major players in the innate immune response
and antigen presenting dendritic cells. Interestingly, while XMRV appears to be able to
infect and replicate in these cells, MLV’s cannot – the reason being that
they cannot infect ‘non-dividing cells’. Ruscetti is currently investigating whether XMRV is
infecting a small number of macrophages/dendritic cells that are dividing.
XMRV and the immune System – MLV’s have a history of producing cancer and neurological disorders in rodents and other
mammals but what about those immunologically disturbed ME/CFS patients? Does XMRV do anything to disturb the
immune system? This study, which looked at how the gene expression in prostate cells changes when they
become infected with the virus, found a good deal of abnormal immune and other gene expression. The authors
stated their findings suggest the virus could have a ‘profound effect’ on fundamental cellular physiology
XMRV and EBV Team Up?– a Spanish team found that XMRV in a significant percentage of EBV transformed (infected?) Cell Lines from
a small group of ME/CFS patients and healthy controls suggested that EBV infected B cells could be a tissue
reservoir for the virus.
XMRV Present in Leukemia and Mantle Cell Lymphoma Cells – Dr. Mikovits and Dr. Ruscetti and others found XMRV in
leukemia and Mantle Cell Lymphoma cells from two patients. The abstract suggested that the development of these
cancers ‘coincides’ with three factors; the growth of the gamma delta T-cells,
XMRV infection and a ‘distinct inflammatory profile’. They appear to suggest
factors could place patients at risk for the development of
these cancers. (Interestingly, neither EBV, nor HHV-6 or CMV appeared to
coincide with cancer development). They also noted that antivirals can help in
HIV derived cancers and that AZT and Raltegravir stopped and significantly reduced previously
rising lymphocyte counts in one XMRV infected ME/CFS patient with cancer. This
suggests antiretrovirals may be helpful in this set of ME/CFS cancer patients.
Dr. Cheny (ahem Cheney’s) Study – Dr. Cheney’s study probably did little to answer any of the more pressing questions about XMRV because the
tests were not done at an independent lab but it should prove quite valuable
when the WPI’s XMRV test is validated. Some of his stats were alarming. Dr.
Cheney has said he probably sees a sicker population and judging
from this sample he probably is; the average duration was almost 20 years! He found XMRV in almost 75% of them. Just as the Phoenix Rising Forums
his patients had a very high incidence of CFS or CFS-like illnesses in their family (45%); 48% had cancer in their families or
themselves and 28% had autoimmune diseases in the family. (One wonders what the norms are.) The most startling fact was
50% XMRV positivity in non-CFS family members. If Dr. Cheney is right this virus is spreading in families.
XMRV Positivity Rates at VIP Dx – In the 7 months between November and May VIP Dx Labs
received 712 samples (about 100/month) from 46 of the 50 states in the US and about 50 from Europe and the UK.
Of those only 35% tested positive for XMRV. The discrepancy between Dr. Cheney’s 75% and VIP Dx’s 35% is surely
one reason why Dr. Mikovits stated the type of patient being tested is a major
factor in the positive rates for a test. Of course, Dr. Cheney with his 20 year
ME/CFS patients was undoubtedly testing a severe subset. We’ll have to wait for
more comprehensive testing of ME/CFS populations to determine just what type of
ME/CFS patient tests postive…It will be fascinating!!!
Children with XMRV – the Ruscetti/Mikovits juggernaut rolled
on with their (fourth?) abstract, this time
indicating that XMRV was present in no less that 82% of 17 autistic children (!) The finding that 16 of the 17 families with
autism spectrum disorder, CFS, FM, Lupus, etc. had at least one member infected with XMRV suggested that it
may run in these diseases, although, of course, much more work needs to be done.
- XMRV International Workshop Abstracts Part I – the abstracts are not the video’s – they should be out soon – but they do give essentials
about the talks and they are INTERESTING.
Those Monkeys – Five Rhesus macaques were infected with XMRV; two of them were sacrificed quickly and the others
several months later. Creating only low levels of antibodies, the immune system did not react strongly to the virus possibly because
it was able to quickly remove the virus from the bloodstream. This apparently suggested to the investigators that the
virus showed low infectivity and virulence, but low and behold when they opened the animals up, they were surprised to find that the
virus had infected many organs and they were able to detect evidence of ongoing replication. Interestingly, the virus hung out in the lymphoid
organs – which give it a clear pathway to the bloodstream. (Dr. Mikovits has suggested that the lymphoid organs could be a
tissue reservoir for the virus). They found that XMRV was also replicating in all the sexual glands
– which, of course, suggests that sexual transmission is a distinct possibility.
XMRV is Different in the Prostate (and the Prostate) – we’ve heard that different XMRV variants may exist in the blood and the prostate but
this study suggested that the XMRV may be different within the prostate itself. This study found different forms of XMRV which, the
authors speculated, could enhance XMRV’s ability to cause prostate cancer (if indeed it does that).
XMRV Is Not Present in Prostate Cancer in the US – While several positive prostate cancer XMRV studies
have occurred this fairly large John Hopkins
study, which used immunohistochemistry, found zero evidence of XMRV in almost 200 samples…But…
XMRV IS Present in Prostate Cancer in the US
– a Baylor study found XMRV was present in 22% of 144 prostate cancer patients –
so much for consistency at this stage of the game. Still a positive report
should trump a negative one, all things considered.
Two more US studies will alternately not find and find XMRV in prostate
Hanson XMRV CFS Study Strongly Positive – This is the first study
to use LnCap Cells (aka WPI) to culture at least some of the blood samples.
Reports from the conference suggested that Dr. Hanson found polytropic MLV’s but
no XMRV but her abstract stated her
study was strongly XMRV positive with XMRV gag sequences showing up in just over half the CFS
patients. The abstract ends “Our results corroborate those of Lombardi et al (Science paper)”!
Dr. Hanson is the first recipient of an NIH grant to study XMRV in CFS patients
and her extensive study to examine the immune factors and the effects of exercise on
XMRV is projected to take at least a year.
Yes, There is XMRV in the UK (and Quite a Bit of It!) – This UK study with Dr. Mikovits in the lead and Dr. Ruscetti the senior author, states that ‘more sensitive’ methods to detect XMRV have
been developed since the
Science paper was published last October. The blood was collected in England and shipped to the National Cancer Institute in
the US. They came right out and said it’s not about the methods – that the most important factor in the negative results in the type
of patient studied (eg, “It’s the patients stupid”) a theory which seems to
have gained some strength lately. The paper states “Since the most important variable in detecting XMRV
in CFS is patient selection” – an interesting statement, if there ever was one.
They used five methods, the most prominent of which was culturing in
the LnCap cells that Dr. Hanson used but they also used
antibody tests and various kinds of PCR tests on different types of cells. The WPI has been
working hard on the diagnostic end as they cited their new antibody tests and new primers that can detect both
XMRV and polytropic MLV env sequences. They also showed, as did the Science paper, that cell free media
from patients contained the
virus (it was present in the blood outside of the cells) and that the virus
could infect other cells once they were placed in it; no wonder Dr. Ruscetti reportedly claimed
his work on the diagnostic end was over and he was moving onto the next stsge of research. This was a very strong study – with multiple
overlapping tests – just as occurred in the original Science study.
A New Method For Detecting XMRV – God knows what this technical
abstract means but apparently Dr. Ruscetti has has developed ‘DERSE’ cells that
can quickly and sensitively detect the presence of XMRV – another diagnostic
improvement in a Workshop that was chock full of them.
‘High Throughput’ Antibody Tests Available – want to test large quantities of blood for antibodies to XMRV? This abstract, if I read it
right, states the authors think they can now do that.
Blood Working Group Has Been ‘Working’ – Not very fast but they are working. They are now very
clear that they have a good test to detect XMRV in spiked vs unspiked whole blood, PBMC’s and plasma. Next step is
looking for XMRV in people!
- Dr. Deckoff-Jones Talks-there’s lots of stuff to consider in Dr. Deckoff’s latest blog
on why the antivirals seem to be working for her and her daughter but not in
some others. As always she takes an admirably sober look at their treatment
situation. She does not recommend that anyone take
these drugs unless they are under a doctors supervision. She notes the risks of
going on a possibly less than optimal drug regimen since we know so little about
the virus at this point and how doing so is a personal decision. (Taking
antivirals in the wrong combinations can imperil the effectiveness of later
treatments). She also believes anyone who starts to take antiretrovirals should
be prepared to be on them permanently.
She provides her entire treatment regimen and notes how
effective a treatment called “Actos” which assists with insulin sensitivity and enhances ovulation and
progesterone levels has been for her daughter,
for whom she says it has been ‘quality of life-changing’. Given XMRV’s androgen
sensitivity there was some concern about the effects of a progesterone enhancer but Dr. Deckoff, herself, is taking testosterone and both of them
feel better. Dr. Deckoff’s statement about endocrinologists
“Endocrinologists as a group seem to be particularly clueless with respect to managing CFS/Lyme patients,
even though hormone depletion is probably pretty universal.”, in my experience, is apt.
This blog is loaded with information -far more than could be covered here. Let’s just end with
her summary to date of her and her daughter’s progress; “All I really know for sure is that
we are X+, we’ve been on antiretroviral treatment since March, on three drugs since May
and we are a lot better. Lyme Disease was a big piece for Ali, probably not for me. We’ve
each gone up at least 30 KPS points since starting HAART. I don’t think it’s possible that
antiretrovirals haven’t helped us. Nothing else we’ve tried in the last few years has
worked, except for Deplin and Ali’s Actos, and I think we can all agree that we were
unlikely to get this kind of improvement from those interventions. But it is possible that
the other things we are taking are potentiating the effects of the drugs or ameliorating
the side effects of treatment. Neither of us feels completely well, especially me.
But we are both hugely more functional. We can only hope it continues.”
- Lancet Takes New Tack
(?) on ME/CFS
– The big 180 year-old British medical Journal Lancet surprised with
a new more viral-based slant on ME/CFS. The editors put two and two together and reported that a recent
study finding increased rates of oxidative stress and white blood cell apoptosis in adolescents with
ME/CFS suggested a viral infection was at work.
Lancet was on shaky ground suggesting that most people who get ME/CFS following
infectious mononucleosis eventually recover but then they went on to state that
ME/CFS was mostly likely caused by pathophysiological problems – a remarkable
statement coming from this journal. They backtracked a bit on that statement
citing the uncertainty about the physical-psychological interactions in ME/CFS
but then argued that research into the disorder should receive ‘high priority.’
Phoenix Rising Forum members found little to like about the editorial but I thought it presented
a major step forward for this particular publication.
Check it out here.
- Nevada Newsline Interviews WPI Vice President Mike Hillerby and Dr. Vincent Lombardi
– After noting that the response from the last radio program was off the
charts Nevada Newsline brought Mike Hillerby back. Mike called the number of
calls and emails he receives almost frightening given how many desperate and
untreated people they indicated are out there.
How it all it got
started – Dr. Lombardi explained just how XMRV/CFS connection got
started. As with many notable discoveries the process was amazing. Dr. Lombardi
was already looking at RNase L (his was the only lab in the US to test for the
RNase L defect in ME/CFS) and was interested in prostate cancer and
contacted Dr. Silverman. While they were at a prostate cancer meeting they ‘threw around’ the idea of
looking for XMRV in CFS patients – something he felt was a kind of ‘pie in the sky’ idea
at the time given how different the two disorders were. Some time later, a
graduate student came into the office
asking for something interesting that he would do it for free… at which
point, Dr. Lombardi, stating that he’d promised Dr. Silverman he’d get the
gave him the samples….and off they went! Soon after that the samples starting
turning up positive. Such were the humble beginnings of this major discovery :).
Dr. Lombardi proved to be an interesting speaker and he soon said something very
interesting – that XMRV has the ‘highest correlation’ of any marker that’s been
found in ME/CFS…. and he would know. As the head of the (former) VIP Dx Labs –
he regularly tested all sorts of markers in CFS. The fact that XMRV shows up in
a higher frequency of people with ME/CFS than anything else is notable; that, in
itself, is a strong argument that it plays a key role in this disorder.
Mike Hillerby noted that they are getting better and better at learning how to find the virus and that their
test is becoming more and more reliable over time. The Symposium that occurred immediately after the WPI’s opening was targeted at clinicians
was targeted at such things as having physicians track which immune parameters
were being disturbed by XMRV. Mike Hillerby said they felt the clinic will be open by the end of the year.
One patient caller noted how phenomenal Dr. Peterson had been in helping him.
Discrepancies in Research Studies – Dr. Lombardi feels that different patient cohorts may very well explain
many of the differences between the studies. Mike Hillerby noted the presence of subtle genetic sequences in MLV’s have
played a role as well. About 85% of ME/CFS patients with well characterized CFS have
tested positive at the WPI.
What about Fibromyalgia? – Dr. Lombardi stated they had seen some FM
patients with XMRV and fit it into the same neuro-immune disease category as
As before Mike Hillerby proved to be an superb spokesman for the WPI
and seems to be able to seamlessly deal with just about any topic. There is much
more in this 50 minute interview –
you can check it out here./a>
Clinical Research Institute of Montreal
110 W Pine Aven
Canada H2W 1R7
E-Mail: firstname.lastname@example.org � /li>
- CFS – the Viral Connection – this webinar with Dr. Komaroff
tommorrow! Dr. Komaroff collaborated with Dr. Alter on the big XMRV study and
has participated in infection research in
CFS for many years. This webinar is a little earlier than most- it starts at 12:30 EDT.
Register for it
- A Time
To Act – Today is several times; it’s Sept 14th, for me personally it’s 3
days after my birthday, it’s 4 days after the WPI Gala Fundraiser, and 327 days
since the WPI published their paper that turned the ME/CFS world upside…but
what time it really is, I think, is A Time to Act. I believe we have an
opportunity present to us right now that may be unique and which, if skillfully
used, could propel us further than we have ever gone before. Our tipping point –
the point at which we give a small nudge that ends up changing everything –
could be upon us. Check it out in
- Mindy Katei’s Take on the Conference –
Mindy was there and she’s provides the first real overview of the conference
itself that we’ve gotten so far. Check it out
- Full Video of Q&A
Session is now available
Myra McClure on XMRV and CFS in an interview for the Interscience Meeting on
Dr. DeMeirleir’s poster on XMRV from the Workshop – Dr. DeMeirleir reports
the presence of reduced CD3 T-helper cells and CD57 lymphocytes and higher C4a,
soluble CD14, serum IL-10, and elastase activity The sample was very
small, unfortunately (16 patients) but the findings are intriguing. T helper
cells are wiped out in HIV/AIDS and Nancy Klimas appears to be finding reduced
cytotoxic killer cells (CD57) in ME/CFS. These are two of the big guns in the
adapative immune response – while they were different from controls they were
still within reference values; they were not ‘shot’ as you see in HIV/AIDS.
It was good to see increased C4a since it has been implicated in the
post-exercise problems in ME/CFS before. Elastase could interfere with a number
of things including blood vessels and it has been implicated in ME/CFS as well.
Other findings were found. Dr. Mikovits has reportedly identified an immune
signature and it will be interesting to see how the two signatures match up.
(Thanks to Rich Van Konynenburg for providing the poster).
- OFFER Conference – I just got back from the OFFER Conference. I’ll do a more formal report later but some tidbits
I got from talking to Dr. Singh and Dr. Vernon.
A Researcher with Culture – At least part of Dr. Singh’s study is a direct replication of the
WPI’s efforts – she is (very carefully) culturing the virus. She said that she
felt researchers should concentrate on the most ‘sensitive’ methods of detecting
the virus that were described in the original paper – and that was clearly
culturing – so that’s what she’d doing. To my mind she basically inferred that researchers that were not doing that were not giving the
authors of that paper a fair shot. The problem with culturing is that it takes six to eight weeks
to culture the virusu and its expensive and labor intensive.
surprised at the difficulty researchers are having. She has been studying XMRV for FOUR years and a relative of it
(Moloney Murine Leukemia Virus) for 10 years – she knows these are tricky viruses.
I asked her if she was having more or less trouble with XMRV than with the
Moloney Virus and she said it was
about the same for both. She could not see any way the WPI’s or Dr. Alter’s
results could be due to contamination.
An Excellent Study – Both Dr. Vernon and Kim McCleary have spoken of her
study in the highest of terms. She is being extremely careful with blood
handling and her test protocols and she is using fresh blood. With 200 healthy
controls in hundred and five CFS patients it’s a very large study and she is
using multiple methods to detect it including qPCR for proviral DNA, RT-PCR, two
types of antibody tests in the culturing. She was in anyin an andShe is building on
past studies and filling in the gaps. She noted, for instance, that the samples
in the healthy controls and CFS patient samples in the original Science study
were handled in different ways and that while the patients came from across the US all the healthy
controls came from Maryland. (In one of those odd coincidence’s all of Alter’s healthy controls
also came from Maryland as well.)
This is not to knock the original study; all studies have their weak points but to illustrate that all studies, should,
as Dr. Bateman pointed out build in each other. Dr. Singh’s patients and controls will come from the
same area and the blood storage methods will be identical for both. This will control for differences in blood preparation
and geographical variations in viral persistence and in viral sequences.
Importantly, with the help of Dr. Bateman, she is also breaking up the patients
into three cohorts depending upon severity.
The XMRV Autopsy Study Is Wrapping Up – She has been working on the XMRV autopsy
study for THREE years. She started it in Columbia and was able to bring it (and
her entire team) over to the Univ. of Utah. (Think of that! Her entire team left
the intellectual backwater that is Columbia to move to that paragon of medical research- the University of Utah
:); she obviously inspires alot of loyalty in her team members). (Let’s hope they were
just shipping slides not corpses). She has been taking samples of every organ in the body, putting it on a slide, and then examining it for evidence of XMRV using her
Immunohistochemistry protocols. (These cause XMRV infected cells to be highlighted.) The exciting news is that the study will be done in the next month and should be published some time around the New Year. I asked if the fact that the XMRV was a hot topic would speed up publication? She said because every journal is afraid of being wrong on a hot topic it would slow it down.
That Rare, Rare Virus – I asked her if a really rare virus could cause such signficant effects as ME/CFS? Did researchers need
to find it in higher levels somewhere else for it to really be doing something? She said ‘No’ and referred to another
retrovirus, HTLV, that she believes could be a model for XMRV. HTLV clearly causes leukemia in some people
but even in those people its found in very low levels. Interestingly, only causes leukemia in a subset of the people that it
infects. Why it causes leukemia in some people but not others is unclear.
Can XMRV cause disease if it’s not replicating? – she noted that several viruses cause cancer
simply by inserting themselves next to oncogenes in a cell’s DNA. I asked if XMRV could disrupt another type of gene simply
by settling down next to it. She thought that was a possibility but couldn’t come up with an instance in which
that had happened with another virus.
Treatment Trials – Dr. Singh again brought up the possibility of treatment trials and even outlined some
paramters and named two companies
she is in very preliminary discussions with. We know she’s gotten some results back from her study. Does the fact that she’s mentioned the possibility of treatment trials twice now tell us anything about her results? We’ll
find out in a couple of months!
Name Change – Will we be getting a formal name change? She
doesn’t think so; for one thing the original discoverer is in charge of naming a
virus and two, she imagined there would need to be much
more consensus on the virus before one would occur.
- Dr. Vernon at the OFFER Conference – Dr. Vernon’s Ph.D was in virology,
interestingly enough. (It was interesting watching her question a patient about
his infectious onset. He presented with an huge swollen gland in the groin area.
She asked did they test for bubonic plague (it is present in California)?
When they diagnosed toxoplasmosis but could not find an antibody to it she
said it might have been a Protozoa with a similar structure then asked if they
gave him antimalarial drugs? She clearly knows her pathogens.
Infectious XMRV and non-infectious MLV’s? – MLV’s have been well studied but not because
they’ve been found to infect humans; they are found in other mammals (dogs and cats, for instance) but, if I got this right, no one has
ever been able to culture MLV’s from humans. So we have a bit of a dichotomy, a clearly infectious XMRV and a not clearly infectious,
at least at this point, group of MLV’s. (Dr. Alter is reportedly trying to code the MLV’s he found.)
The Director Drops In and Stays…. – Dr. Vernon was astonished to see the
Director of the NIH drop into the XMRV International Workshop and then STAY. She said he was there in the front row and asking
questions for 75 percent of the Workshop. She has been to many many conferences over the years and she’s
never seen that before.
The Lipkin-ME/CFS Connection – is much stronger than we thought. She appears to have known
Dr. Lipkin for quite some time; she said he first came across ME/CFS patients in the early 1980’s and that
he’s always thought CFS was caused by an infection. Dr. Lipkin is also collaborating with Dr. Montoya
on his broad look at pathogens in ME/CFS. The Columbia ME/CFS connection is certainly intriguing; there’s
Dr. Lipkin, Dr. Singh (before), Dr. Racaniello and Dr. Goff.
Putting ME/CFS on the Map – Dr. Vernon is excited about XMRV and doesn’t know how
it’s going to turn out but she is clearly very happy about how it has put CFS on the map; she clicked off
the number of powerful groups that are interested in ME/CFS because of XMRV; the NIH, Red Cross, big Pharma, CDC and FDA. She
thinks it has engineered a the most fundamental change in how ME/CFS is viewed.
‘Look Back’ Study – CFIDS Association of America is working with the Red Cross to do a
‘Look Back’ study to examine old blood stocks and help determine if or how much XMRV is transmissable
through the blood.
- Dr. Racaniello Talks – Coming back from vacation, Dr. Racaniello talked about
Dr. Alter’s paper. After noting that it provided “support for the involvement of murine retroviruses in CFS”
he stated Dr. Alter’s ability to find MLV’s in the same patient 15 years later was ‘important’. He felt
the most important finding was the discovery of the polytropic MLV’s. He, like Dr. Vernon, described them
not as ‘variants’ of XMRV but, despite their genetic similarity, as entirely different species. He noted that
XMRV is a combination of polytropic and xenotropic viruses (while the MLV’s are all polytropic). (We’ve heard
how much these viruses like to intermingle).
Dr. Racaniello then echoed Dr. Mikovits argument that researchers focus on a narrow slice
the genome “could, in part” explain their inability to find murine leukemia viruses in ME/CFS.
Then he suggested that the
ability of Alter/Lo group to ‘readily’ find MLV’s in both plasma and blood
suggested that the WPI might need to adjust their primers as well, since that indicated culturing is not necessary
as the WPI proposed. (Dr. Mikovits, of course, has stated that the WPI long-ago
found these ‘variants’ or what Dr. Racaniello and others firmly refer to as
similar viruses but separate species.)
Different Primers – A comment on the blog by Jacqueline was intriguing. She noted that nowhere
in the original paper did it state that culturing was used in the PCR (which is
true – the PCR test in the original paper did not
use culture; another part of the paper did. In fact in their official statements
the WPI has never said that culture was absolutely necessary; it’s simply the
most ‘sensitive’ way of finding XMRV at this point). After taking a close look
at the ‘inner’ primers the Alter and WPI groups used she found a small
difference she felt might explain why the WPI missed the MLV sequences (if, in
fact, they did) but did not explain why Alter was unable to pick up XMRV. Dr.
Hansen, reportedly, also found polytropic MLV’s but no XMRV in her samples.
Meanwhile, of course, we had some studies pick up XMRV….it’s clear that we’re
in a (rapidly, although it doesn’t seem that way) evolving field and that these
issues will get cleared up over time. The most important conclusion of the Alter study was that, just as in
the WPI study,
murine leukemia retroviruses were highly associated with ME/CFS and not with controls.
Jacqueline’s Blog – Jacqueline is a medical librarian with some experience
in this field. She’s written a series of rather technical blogs on XMRV. Warning
– she’s not been particularly happy with the WPI, in fact, she’s not
particularly happy with anyone (although she did like the Alter paper); what she
offers is a deeper dig at the technical aspects of the studies than most
- XMRV Workshop
Q & A Transcript – (Somehow)Global Action managed to
get together a
Transcript of Q & A sesion at the Workshop. (How do you do that from a
live feed??) However,they did it they did it quickly and well.
Check it out here.
- No ‘Flip’ Yet – The Workshop did not out to be the place where the
research world flipped from worrying about how to find the virus to figuring out
what it does and how it does it. According to one report Dr. Ruscetti said he,
at least, was turning his
attention from diagnosis to pathogensis but it was clear that many others were
not. The Q&A session revealed a hard-nosed bunch of researchers who want to get
matters nailed down before they move on. The NCI chiefs response to Dr.
Ruscetti’s question about more funding (none planned) indicated that the
Institute was waiting for the testing issues to get ironed out before it would
as well. Indeed, the second really major bit of positive news (see below for the first), thus far,
to come out of the Workshop was the creation of another diagnostic task force
under the direction of an ace pathogen detective Dr. Lipkin. XMRV continues to be hung up – at least in
the views of many of these researchers – on the horns of the disparate PCR
Slow Progress – Dr. Stoye had hoped to have answers by now.
With three more negative and three positive studies reported Dr. Coffin
stated “we�re still in a zone of chaos where…. we don�t have agreement on
almost anything in this. We have to work toward that right now”
Interestingly, Dr. Coffin tried to damp down what he appeared to feel were
overly exuberant expectations of success, stating that he felt, at this
still early stage of the game, that things were moving about as expected.
“It�s really quite a short time. It takes a long time, to set up, say to set up
the blood working group panel, it�s been probably six months of talking and deciding
and so on before we began to get samples really in� so it�s only couple of months that
we�ve been working on that. So I�m quite optimistic that say
within the next year there will be a synthesis of this to
the point where not necessarily everyone�s using exactly the same assay” Others felt results would appear
more quickly. Dr. Stoye, in fact, expected to get results ‘very, very quickly’ (whatever that means
‘researcher time’!) and others have stated they believe the Blood Working Group to have some standardized assays
ready by Christmas.
Dr. Mikovits argument that the human retroviruses have been, in the early stages of
our understanding of them, difficult to assess using PCR and that antibody tests
are more appropriate appeared to fall on deaf ears – at least in that group. Dr. Sing, however,
noted how difficult it was to get human papillomavirus (not a retrovirus) nailed down using PCR, and yet how much progress they made
when they finally did do that: “if we look at the HPV research, in the early age of
HPV research, there was a struggle of HPV detection and once that was validated and
clear, there was tremendous progress in HPV research and then there was the HPV vaccine development”.
ME/CFS Patients Being Undercut? –
Dr. Mellors, the Chief of Infectious Diseases at the Univ of Pittsburg, felt that
ME/CFS patients concerns were being undercut by a Blood Working Group focused
mostly on the safety of the blood supply. He argued that a much more extensive testing
a neutral party disseminating samples to multiple laboratories using their own
methods should be underway. (This appears to be identical to what Dr. Enlander has proposed
and is reportedly working on) Dr. Holmes of the Blood
Working group stated they were getting all their samples from the WPI but that they were
from a wide geographic area and Dr. Mikovits backed him up on that. Dr. Sing
agreed on the need for more widespread testing and also descried the inability of
the research community to work together (something the research community has been descrying
about itself for about six
months) stating “All of this is dependant on highly accurate, sensitive,
specific assays. So some sort of coordinated effort among these laboratories using different assays, different platforms, I think
that will make tremendous contribution to the
field of XMRV research. So I really encourage you to work together…some kind of collaboration and coordination I think would really make
this field move forward much faster, and I am looking forward to that.”
THE ANSWER is At Hand? – In response to a question about the effects different
‘collection and storage’ techniques might have had on study results, Dr. Mikovits
jumped in with an answer that threatened to make many of the questions asked
above moot. It seems that just in the past few weeks, no doubt spurred on by the
Alter/Lo findings, that the Blood Working Group may have uncovered a key problem plaguing some of the
negative studies: “we have learned literally in past 2 wks in the BWG that
processing may be a key and we may have found an opportunity to have a processing
protocol where everyone would
at least find viral RNA in plasma and blood products without culture.” What
an odd thing if something as simple as ‘processing’ problems (blood handling and
storage?) were at the heart of all this mischief. Somehow, however, the discussion veered off onto
another tangent after Dr. Mikovits startling response and we heard no more of this!
Treatment Trials – a good part of the Q&A was taken up on the treatment
trial question with Dr. Coffin and Dr. Stoye coming out strongly against even
small treatment trials until they had found a way to measure viral load using
quantitative assays. After at first refusing to be drawn into the question of
the validity of anti-retroviral treatments by a question from Hilary Johnson,
(Dr. Mikovits is not a physician) Dr. Mikovits later argued they could learn
alot now from treatment trials using immunological measures. Of course treatment
trials in CFS always use accepted qualitative clinical measures of
functionality, etc. and there are several of them but they are apparently too qualitative for the virologists at that table.
Mindy Kitei started off the first clinical trial question section and then came back again later, questioning
whether certain groups really wanted to find the virus. She pointed out that the
CDC used the same German research unit to validate their results that was unable to find XMRV in prostate samples…(Hmmmmm).
She asked – why not send them to the Cleveland Clinic instead…which seemed a
reasonable question but the implications of it disturbed Dr. Stoye greatly,
leading him to respond “I think we�ve heard enough of this particular line of questioning. I think nobody in
business is trying to get a negative result � it�s in nobody�s interest.”
Really, they both have their points. It’s
certainly not in the interests of Dr. Wessely or Dr. Kuppeveld or the CDC CFS
Research group to find a retrovirus. On the other
hand it’s entirely in the interests of retrovirologists to find one whether they work at the WPI, the CDC’s
HIV division or
elsewhere; another human infectious retrovirus (there are only two others) is huge news for their field.
Now that some retrovirologists have staked out their ground on XMRV issue, of
course, we have a different set of
conflicts to worry about…..
The Cohort Question Again (and again and again) – One physician asked how accurate diagnoses can be based on
physicians that may either place patients ‘in’ or ‘out’ of ME/CFS based on
subjective criteria. Dr. Mikovits agreed stating that if “you look for various immunological defects rather than just subjective defects” you get better results. It was the
idea of an immunological abnormality ‘filter’ that raised so much ruckus in the
Science study. The WPI backed off on those stating those immunological
abnormalities were not
a requirement and now here
they are again. Both Dr. Mikovits and Dr. De Meirleir, interestingly, stated they’ve found immunological signatures in
XMRV infected patients; it’ll be very interesting to see what they are.
The Lo/Alter Results – Dr. Coffin readily acknowledged the validity of the Alter findings but
was careful to ensure that everybody realized that the only virus that has actually been
captured and sequenced is XMRV stating “I think before we start referring to a bunch of different viruses we really need to have viruses that go with those sequences. We can say there are sequences there that look like endogenous MLV�s, maybe a little bit different
from them. But we just don�t have a virus yet to go with them.” He agreed that Dr. Lo’s may have
been on to something when he suggested that the CDC and other groups were unable to find
the MLV’s because they were using a ‘leader sequence’ that didn’t match up with them. Looking at that
will help clear up whether other MLV sequences are present are ME/CFS. Dr. Alter/Lo are in much the
same place Dr. Mikovits, Dr Ruscetti, Dr. Lombardi and the Cleveland Clinic were in a year and a half
ago when they had sequences but not a complete virus. Dr. Alter is reportedly trying to culture the
MLV’s they found in their study and completely sequence them.
Funding, Funding, Funding – Dr Ruscetti reminded everyone that a little thing called ‘funding’ was necessary
to carry on this work – something he’s clearly worried about – stating ” But what
fuels that is a practical thing called funding. So you�re involved in the extramural program of the NCI.
What would it take for the NCI to increase funding in this area” and getting that standard response from
someone who must, at least in some manner, be his boss: yes, we’re all so interested in this subject and
isn’t it great that we’re having this workshop (doesn’t that demonstrate our interest?) and then stating that no’
new funding directly devoted to XMRV will be coming until the testing problems are clarified. In fact, even then
then all he would say was that he ‘suspected’the NCI would then’look’at the issue: “As things develop and it becomes a little clearer
what�s going on I think then certainly I would suspect that the NCI and NIH are
going to look and see if there are things
that would be appropriate to do – and if the money is available.” Interestingly, he said the NCI has not had
alot of grant requests, something an audience member suggested indicated that researchers are not willing to put alot of effort into
a subject they still have questions about.
Dr. Coffin echoed the fact that the NCI has not put a dime of intramuural funding into XMRV, forcing researchers to
divert their own resources into exploring- something that says something very special about
researchers and the
system they work under – but which also has its limits.
NCI has not put any extra $ intramural money for this purpose � yet an enormous amount of work has been done
and a lot of funds have been diverted by all of us from our previous projects into this area. I think this is remarkable testimony to the resilience of American, European, international science, that, in fact that
we can do this without the necessity for instantaneous top-down funding. However the momentum on this will tend to run out after a bit without additional money being put into it at some level or another.
So it�s very important to sustain the momentum that we have so far.”
Why is it So Darn Difficult? – Dr. DeMarzo at Johns Hopkins asked
why, if XMRV plays such a central role -it was so darned difficult to find using
all this ultra-sensitive PCR technology? Dr. Mikovits suggested that
it wasn’t that surprising at all investigators should rely on
‘complementary methods (eg serology (antibodies)). Dr. McClure said she’d happy to grow the virus
if she could find it but she couldn’t find it using PCR or serology and then “I don’t know
what else we could do” which was a kind of amazing statement given the Blood Working Group
and others appear to
have found lots of ‘other things to do’. Dr. Ruscetti then cut in, making Dr. Mikovits’ point –
that you cannot rely on PCR alone – in even stronger fashion stating “Negative PCR is not
a stand-alone assay for detection of this virus in clinical samples.” Nothing was resolved in that little exchange which
threatened to get hot and the room moved on.
“The Disease Causes the Virus”?
During a question about immune abnormalities Dr. Coffin made the interesting
suggestion that the virus is present in everyone and that the disease allows it to show up in more sickly people.
“I mean it�s still possible to entertain the idea that the disease causes the
virus, and not other way around in a sense… or makes visible a virus that�s
actually very prevalent, but it�s really such a low level in some, couple of
cells somewhere in people, it only comes up because of the conditions
surrounding these diseases.”This is a question that can only be resolved with
validated assays and more testing in more disease groups.
Dr. Mikovits, however, noted that the envelope of gammaretroviruses produces
neurotoxins and that the HIV retroviral model – one retrovirus knocking down a
part of the immune system – causing pathogens to flourish, fit ME/CFS pretty
Thanks to XMRV Global Action for the transcript!
- Workshop News – The Workshop continues to scintillate….More evidence
that the NIH is getting involved; the Director of the NIH, Dr. Frances Collins
kicked off the Workshop – that was news – and then apparently left but is
back….in a front row seat viewing the CFS section…
- A negative study deciphered? Huber’s negative XMRV study came under some
question because of speculation her use of ‘hepanarized blocks’ might have
blocked her ability to find the pathogen.
- A positive study explained? – Dr Lo apparently held forth on ‘several
conditions’ that could have impacted other researchers ability to find the
- International XMRV Workshop Exceeding Expectations – In terms of impact on policy the International
XMRV Workshop is exceeding expectations. The big news is that the NIH tagged
NIAID Chief Anthony Fauci, himself, to oversee a major study on XMRV and CFS.
Anthony Fauci is a major, major figure – he is the HEAD of the NIAIDl
(National Institute of Allergy and Infectious Diseases) – and
his appoinment indicates what a hot-button issue the NIH believes XMRV in. Dr.
Mikovits has complained how the NIAID has ignored XMRV thus far….well, they’re
not ignoring it any longer. By appointing Fauci they are attempting to
demonstrate to the world how serious they are about the subject
Anthony Fauci,But Anthony Fauci did a
however, has been no friend to ME/CFS – in fact, he’s been considered a major
problem for years. He headed the NIAID when ME/CFS
was kicked out of the Institute ten years ago, an event which lead to years of
research declines as the program slowly disintegrated in the backwater that is
the little Office for Research on Women’s Health and he has been utterly
resistant to attempts to increase funding.
very interesting thing when he turned the research project over to Ian Lipkin
at Columbia University, an ace pathogen detective, who was already rumored to be
studying XMRV in ME/CFS. When asked by Amy Dockser Marcus why the conflicting
results thus far he cited different types of patients, sample preparation and
methods. His study will include testing samples from different areas of the
country at the WPI, FDA and CDC. Here’s some info from the Marcus article
The new study, Lipkin says, will involve fresh blood samples from 100 CFS patients and 100 similar,
but healthy people � 25 of each group from four different sites around the country, to provide
geographic diversity. The samples will be processed, blinded and sent to the FDA, the CDC and the
Whittemore Peterson Institute, which led the team that published the original Science paper. If a
lab finds a sample is positive for XMRV, further tests will be needed to confirm the result. If one
lab finds a positive sample but another lab doesn�t, the same samples can be shipped again, with a new blinded
code, to be tested again. �If you get the same result, it is valid,� Lipkin says.
Ian Lipkin – who is Ian Lipkin? Ian Lipkin is a pathogen hunter who has tracked down some of
the ‘hottest’ pathogens of recent years including the West Nile Virus and SARS. More importantly
he is known for his creation of cutting edge techniques to uncover new and emerging pathogens. In short, he is the ‘tip of the spear’
in pathogen discovery – the man they send out get a hold of new bugs. He’s also
heavily involved in viruses that effect the brain and in autism. One of the premier pathogen hunters on the planet,
his appointment indicates the NIH’s has finally gotten serious about XMRV….
This is what you would expect when the top retroviral Institute in the world
gets moving. Here’s from Wikipedia on Dr. Lipkin:
A physician-scientist, Lipkin is internationally recognized for his work with West Nile virus and SARS, as well as advancing pathogen discovery techniques by developing a staged strategy using techniques pioneered in his lab. These molecular biological methods, including MassTag-PCR, the GreeneChip diagnostic, and High Throughput Sequencing,
are a major step towards identifying and studying new viral pathogens that emerge locally throughout the globe.A major node in a global network of investigators working to address the challenges of pathogen surveillance and discovery, Dr. Lipkin has trained over 30 internationally based scientists in these state-of-the art diagnostic techniques.
Lipkin is the Director of the Northeast Biodefense Center, the Regional Center of Excellence in Biodefense and Emerging Infectious Diseases comprising 28 private and public academic and public health institutions in New York, New Jersey and Connecticut. Within this consortium,
his research focuses pathogen discovery, using unexplained hemorrhagic fever, febrile illness,
encephalitis, and meningoencephalitis as targets. He is the Principal Investigator of the Autism Birth Cohort, a unique international program that investigates the epidemiology and basis of neurodevelopmental disorders through analyses of a prospective birth cohort of 100,000 children and their parents. The ABC is examining gene-environment-timing interactions, biomarkers and the trajectory of normal development and disease.
Lipkin also directs the World Health Organization Collaborating Centre for Diagnostics in Zoonotic and Emerging Infectious Diseases, the only academic center, and one of two in the US (the other is CDC), that participates in outbreak investigation for the WHO.
In 1989, Lipkin was the first to identify a microbe (Bornavirus) using purely molecular tools. Lipkin was employed by University of California from 1990-2001. He began as Assistant Professor in the departments of Neurology, Anatomy and Neurobiology, and Microbiology and Molecular Genetics. He advanced to full professor in under six years and was named as the first Louise Turner Arnold Chair of Neuroscience before moving to Columbia University.
In 1999, Lipkin led the team that identified the West Nile virus in brains of encephalitis victims in New York State .
In April 2003, he sequenced a portion of the SARS virus directly from lung tissue, established a sensitive assay for infection, and hand carried 10,000 test kits to Beijing at the height of the outbreak. As the first foreign consultant to gain the confidence of the Ministry of Science and Technology and the Chinese Academy of Science he was named Special Advisor to China for Research and International Cooperation in the Fight Against SARS and was instrumental in promoting disclosure and outside collaborations in infectious disease research and public health management. His position recognizes this extraordinary service, wherein Lipkin and his colleague Thomas Briese, traveling to Beijing at the height of the SARS outbreak at the request of the Chinese government, hand-carried 10,000 test kits to be used for identification and containment of infected individuals, and coordinated the national research efforts with Chen Zhou, the current Minister of Health of China.
Check out a new article on Phoenix Rising: NIH Steps Up to the Plate – for
more information on Ian Lipkin and the new study
Dr. Peterson and ME/CFS Patients Meet with NIH Officials Before XMRV Meeting
– in yet another indication that the NIH may finally be taking both XMRV and
ME/CFS seriously – Bob Miller lead a group of patients into an hour long meeting
with NIH officials.
Back On the XMRV Beat – not surprisingly Amy Dockser Marcus at the Wall Street
Journal was out quickly with the story.
Click here to check it out.
- Tweets from the Cleveland Clinic – Cleveland Clinic personnel
are twittering and they’re coming up with some interesting stuff. Check out
their Tweet’s here
- XMRV Workshop Videocast Tomorrow-
the closing Q&A section – perhaps the illuminating part of the
conference will be videocast live tommorrow at 5:15 EDT. Andrea Whittemore posted a note
stating that “Things will finally be put to rest during Dr. Ruscetti’s talk on
What an acknowledgement of Dr. Mikovits and the WPI’s
work this Workshop is! Ten months ago no one was interested in XMRV. Ten months
ago who would have dreamed the Director of the NIH would be opening an workshop
focused partly on ME/CFS or
that a Lasker Award winners or other luminaries would be
We all want the answer NOW but it’s utterly astonishing what’s been
accomplished in such a short time. Here’s to a Workshop that, as Dr. Collins put it, asks
‘penetrating questions’ and comes away with empowering answers that ultimately
lead to a resolution of this disorder.
- Head Honcho of NIH To Start Off XRMV Workshop – It was clear in the Science
paper that XMRV was
attracting a caliber of researchers we haven’t seen very often from; the
Ruscetti’s and the Silverman’s of the research world just hadn’t been spending much time
in the lab on ME/CFS.
that the Director of the National Institutes of
Health – the big honcho himself, Dr. Francis Collins, decided to bump what’s his
name off the podium, and deliver the opening address for the XMRV Workshop
himself, appears to have taken the ‘name game’ to a whole new level. Yes, it’s
just an opening address and that in itself means little but he wasn’t on the
ticket earlier and it’s not hard to think someone hasn’t been whispering in his ear
“This is one you want to get on top of”. One wonders what he will be saying about ME/CFS
and what other surprises the Workshop might have in store..
- The XMRV Black Hole – The UK, at this point, appears to be a kind of black
hole for positive information on XMRV; the positive stuff goes in and a negative
interpretation gets quickly shot out. The UK Science Media center presented two
short critiques of the findings that were, well, completely critical.
Neither Dr. Weiss, nor Dr. McClure could say anything good about it and focused
on the abscence of ‘blinding’, the four negative studies, etc. Dr. McClure was
‘mystified’ by the ability of both the Alter group and the WPI to find MLV’s
after only the first pass of the PCR yet both Dr. Mikovits and Dr. Lo have
pointed out that the different primers they used could have accounted for that.
Almost all the parties, both pro-leaning and anti-leaning XMRV, agree that more
study is necessary to nail down what has been causing the disparate results.
With several positive studies reportedly about to get disseminated one wonders
if that question will begin to be answered to most researchers satisfaction.
- The XMRV Polls -as we await the results of XMRV Workshop let’s take a look
at the XMRV Polls on Phoenix Rising. The Combined PCR/Culture poll was begun
with expectations of high participation yet almost 10 months later only 33
people had taken it. Of those 60% had tested positive to at least one of the
tests. With 40 people presenting results on the Culture test
55% percent tested negative. The Antibody Poll was started in April and five months later only 12
people have taken it; 59% testing positive and 41% negative. Because the antibody test was likely taken
by people testing negative to the other it could bump up the final percentage of positives significantly.
The small polls suggest, though,
that while many people are testing positive a chunk of people with ME/CFS are
testing negative at this point. Severely ill people do not appear to be testing positive more often
than moderately ill people. What the final, validated XMRV test will
show, of course, is unclear.
- XMRV and Lyme Disease?
– XMRV has been creeping into other disorders from almost the day the
Science paper came out. Dr. Cheney recently stated in the intro to one of his
‘pay-for’ articles that in his patients Lyme does not appear to exist independently of XMRV -which suggests to him that they are
interconnected in some way. Now Daffodil on the PR Forums reports that XMRV is on the agenda of a big Lyme conference in October.
The disorders XMRV is connected to will be an increasingly important factor as other questions get taken care of. Will
it be associated with other pathogens? Does it ‘open’, so to speak, the door for them? Does it have a special
connection with herpesviruses in CFS or is it associated with other pathogens?
Plus the all important question – where does XMRV stop?
The first big step for XMRV, of course, though, is getting recognition from
important opinion-makers in the research world, such as Dr. Alter, that XMRV is
definitively associated with ME/CFS. Once that question is erased in the
research community it can move on….With the
cautious tone overall from the traditional research community, we’re definitely
not there yet…(Where is Dr. Racaniello’s blog on the Alter report?)….
- Dr. Deckoff-Jones Digs into the MLV
research – check out her blog for lots of good, if technical, information on
MLV’s. She notes that Dr. Sandra Ruscetti has been studying them for over 30
years. (What a strike of luck that Dr. Mikovits just happened to be deeply
associated with the Ruscetti’s…How does that happen? Sometimes the gods do
smile on CFS.) It’s not easy reading (she says, “Yes…It is harder than
rocket-science” :)) but there’s alot there.
- XMRV Workshop – We know that positive studies are being ‘released’ at the
Workshop. What we don’t know is how strong each of them is and what kind of
difference they will make….Will the big-wigs be swayed by a study by physician
Paul Cheney? Probably not. Might they by Rebecca Hansen? Probably more so. Will
they by Dr. DeMeirleir? Judging from their reception to his RNase L work –
not. They’ll be most interested in very rigorous studies that dot all their i’s and
T’s and it will help greatly if they come from major figures like Dr. Alter. The
reception to the positive studies will be interesting. Will things begin to flip
at the Workshop or just get better?
- Webcast of Workshop Final Q & A: Here’s the panel for the final Q&A session.
Thank god, Dr. Mikovits – who is basically responsible for the Workshop
occurring at all – is on the panel. (Could you imagine??) Thanks to Bob
for providing this.
It looks like a good panel for XMRV with an NCI figure,
Dr. Coffin and Mikovits participating.
The Q & A panel will consist of the
following experts in the field of XMRV:
Don Blair, National Cancer Institute, Bethesda, USA
John Coffin, Tufts University, Boston, USA
Jerry Holmberg, US Dept. of Health and Human Services,
Judy Mikovits, Whittemore Peterson Institute, Reno, USAThe session will be chaired by:Jonathan Stoye, National Institute for Medical Research,
ME/CFS Patient Reacts Negatively to Antiretrovirals Bought Online – we
haven’t heard of many people really suffering under ARViral drugs but RandalBond
on the Phoenix Rising Forums had a very hard time with them and stopped them and
continued to decline. (He has not been tested for XMRV but thought he surely had it given
statements on prevalence he had heard. He did the antiretrovirals unsupervised and bought them online –
definitely not a good idea to go this route!).
Check out his story here.
- CFIDS Association Talks XMRV with the Experts
– the CAA grabbed a variety of different experts
and put some questions to them regarding XMRV. Check out this interesting
A Session here.
- The Workshop WEBCAST!
– Filfa4 on the Forums pointed out there will be a webcast of the
final Q and A session that is billed to last 2 hours! The Q & A sessions are often
the most interesting parts of any conference; this one begins on 5:15 EDT on Wednesday,
Sept 08th. Check out
the link here
Rrr on the Forums followed up with the NIH and learned that
all portions of the Workshop will be filmed and the
presentations will go up, subject to the presenters permission, on the NIH
website 2-3 weeks later so it’s concievable we could have most of the Workshop
available for viewing. Thanks for Filfa4 and Rrr for being alert and getting us
– It’s a two day workshop. It starts out with basic
stuff; where the virus integrates itself into the cell’s genome, which types of
mice may contain XMRV-like sequences, and then there is a presentation on a
‘novel gene product’ of XMRV – which means? what – a protein?? In any case it
appears to be something new to science which is always interesting.
In the next session there is a talk on animal
‘models’, which are animals researchers
use to give XMRV to and then study. Animal models are critically important to understanding how
pathogens function and its good to see researchers focusing on animal models so early.
Dr Bishop will
talk on ‘Host Restriction Factors’ which are factors in our cells that restrict
viral replication. These factors may be one reason why XMRV appears to be different in prostate cancer
tissues and the blood. Next comes a VERY INTERESTING lecture.
Dr. Villinger then talks on why XMRV Induces a Chronic Replicative Infection in Rhesus Macque Tissues and
But Not in the Blood”. We’ve been wondering where, if any place, XMRV is replicating? We know it
hardly happens in the blood but is there a tissue somewhere (besides the prostate) where it’s
growing away? Dr. Villinger will tell us where in the bodies of these macaques XMRV has found
a home. Is it the nervous system? (Wouldn’t THAT be exciting/appalling…) How
about the lymph nodes? The blood vessels? These are macaques, not humans, but
this presentation could have profound implications.
The next talk by Dr. Kazak will fit in perfectly here because he will look at different
variants in the XPRI receptor that XMRV uses to enter cells. These variants may determine which cells
XMRV can get into and cannot. The next day starts out with the prostate cancer series which we will bypass, except to say
that Dr. Singh is giving a lecture on pathogenesis. The section on CFS comes next.
Dr. Mikovits and Dr. Ruscetti chair the section and he (not Dr. Mikovits) will lead off with a talk on subject he was hardly aware of until two years ago – chronic fatigue syndrome. Dr. Hanson
is next. Thus far she has the only CFS/XMRV NIH grant that has been funded. It’s
a full ROI grant which means (a) that she must have had some preliminary data
and (b) that data must have been positive – so here we appear
to have the third positive XMRV study to appear. We
know she is studying Dr. Bell’s pediatric patients (or formerly ‘pediatric’ now
middle-aged patients) and that her rather complex study wll look at a variety of immunological and other features. One interesting question will be if she has
blood samples from 25 years ago from these patients.
Right next to her
Dr. Huber will presumably report on her negative study – an
interesting juxtaposition indeed. Dr. Lo will report on the Alter/Lo positive finding and then we believe we’ll have
a second positive study report by none other than Dr. Mikovits herself.
This appears to be the Invest in ME/WPI UK study that used an independent lab to
replicate the WPI’s results. The title of this one is intriguing “the Detection
of Infectious XMRV in the blood of ….in the UK”. One wonders if the inclusion
of the word “infectious’ in there could mean anything special about this study?
The Assay development section will start off by a lecture by a man who’s
never been able to find any XMRV in patient’s blood – Dr. Switzer of the CDC. After the Alter/Lo
study and the FDA’s statement that ‘sample preparation’ could’ve played a role in the inability of
the CDC to find XMRV this lecture could be interesting. (Dr. Vernon’s test tube comments come to mind)… Could
Dr. Switzer tell us
something surprising here? aka ‘we made a mistake?’.
Dr. Bagni will represent the WPI as she
explains how to produce an antibody test for XMRV then we’ll get good news about the development of
XMRV immunoassays for large scale population studies. Finally Dr. Kearney
– who may be part of the Blood Working Group will talk on his success in finding XMRV in blood products.
(Things are definitely moving forward on the diagnostic front.)
In the last session on Epidemiology the Bannert lecture will indicate to us that he did not find XMRV but he also shows that the bug can infect blood cells
– which sounds that he’s replicated
a key part of the Science paper (!) but still can’t find the virus…We’ll have another opportunity for
another positive study when Dr. Blomberg talks about his search for XMRV in Sweden. Finally it appears that another
member of the Blood Working Group will report multi-laboratory evaluations of different XMRV assays.
Dr. De Meirleir is believed to have a poster providing the results of another postive study
and the identification of an immmunological signature associated with XMRV infection. At this point
it appears there may be at least three positive studies and possibly four.
The 2-day Workshop indicates that
Science is marching forward very quickly; indeed at lightspeed compared to what we are used to. If XMRV wins out this could be just the beginning; the medical research establishment (contrary to our experience) in the US,
after all, is vast
Months ago, Dr. Klimas reported that retrovirologists were hungry for something new…Might
ME/CFS go from doormat to hot research ticket? That would be something
– how to explain what appears to be a near virtual media blackout on the Alter
study in the UK? Several UK residents have reported looking fruitlessly for any
mention of a paper that made it to several hundred other media outlets
elsewhere. Somehow the story didn’t even make it onto the pages of the vaunted
BBC. (How does this story make it to Iran, of all places, and NOT the UK?) One
expects the Western media to display some independence but it seems that the
British media, at this point, is only interested in one kind of story on ME/CFS
and that story does not involve pathogens. Yes, they will cover a pathogen story
if they can’t ignore it (and downplay it) but if they feel that they can ignore
it, then it appears that they will. It’s amazing (and appalling) from the US
side to see an entire country’s media en thrall to one belief system regarding
CFS and it definitely messes with one’s idea of an informed and objective media.
What a rough ride UK patients have…..
As we watch the media in the US we can also see patterns forming. The Wall Street Journal has
a journalist who appears to be very interested in CFS and she has made a difference there. The NYT does its
generally thorough job and they’ve been giving XMRV and ME/CFS a real shot
throughout. The Chicago Tribune, on the other hand,
has focused on negative aspects. It appears that much matters on which journalist gets interested in the subject and what their
own particular slant is.
The message is- cultivate those reporters if you can.
NIH Goes Public on XMRV – The NIH finally threw its hat in the ring on the
new XMRV findings. In the NIH Research Matters section the official NIH release
starts off with a bang “New research supports the idea that viruses may play
a role in chronic fatigue syndrome (CFS), a debilitating disease that affects
millions of people nationwide” What a nice sentence that is; it fits in viruses,
debilitating disease and ‘millions of people’;
they almost make it sound like we have a major problem here….Did Fauci
groan when he saw this? Is he starting to wonder how he’s going to explain how
under his direction the NIAID has basically ignored CFS and it’s millions of
retroviral infected patients for decades? How he is going to explain his paltry
budgets over the past 25 years for the millions of ill patients? One fervently
hopes that at some point he’ll be pressed at some point to explain just that. The neglect of the ME/CFS community
by the federal goverment borders on being criminal and hopefully the bureacrats in charge
will be held to account for their apathy and negligence. (Can you see a 60
minutes program lighting these people up? I can).
In any case the article illustrates that
no matter what happens with XMRV, CFS should now be associated in many people’s
minds as something that’s ‘debilitating’ and common. Overall its a nice little
be characterized as ‘friends’ and I really blasted them in the last buzz post but
that’s all the more reason acknowledge them when they do shake off their
negative mindset and stepforward. I was informed that
it was none other than the NIAID that helped fund Dr. Alter’s work. They definitely get two stars for that, and
hopefully, over time, we will see much more.
– please check it out,
give it some hits and watch it spread.
The next weeks CFIDSLink is reportedly going to feature
Q&A’s with professionals (including Dr. Alter) about XRMV. One question
we know Dr. Alter will be answering is if he found any MLV’s in the CDC’s
samples. If he didn’t then either the CDC’s ‘CFS’ group is not just different
but amazingly different from the Komaroff’s group of CFS patients in the Alter study OR the
CDC has a problem with ‘sample preparation’. It was Dr. Vernon who pointed out
that the CDC’s test tubes might not have been right for virus collection. When a
virus is as rare as XMRV appears to be in the blood it might not take much to
knock out what little is there. What is going on? Maybe by Workshop we’ll
CDC will be presenting their lecture on assays just after Dr. Alter’s assays
found MLV’s….THAT will be interesting. Kate Bishop who basically cracked an
essential part of the XMRV mystery for Dr. Mikovits will be there. THAT is
encouraging. We believe that at least two positive XMRV studies will be reported
there and Dr. DeMeirleir will report that he’s found distinct immune
abnormalities in XMRV infected patients. THAT will be outstanding. Other
researchers will, no doubt, be deep in discussion about MLV’s and XMRV and how
to piece together all these different. THAT will be intriguing. Dr. Singh, from
what I’ve been told, from someone would know, may have the best XMRV studying
going and she’s talking as well….and at the OFFER Conference on Sept 11th in
Salt Lake City. THAT will be illuminating.
This is the hot ticket in
town! The Workshop filled up quickly and is no longer open but congratulations
to those CFS patients who managed to get in (And boo-hoo for us (me!) who
didn’t)….We look forward to your reports!
Study – while being careful to cite issues that need to be cleared up
Medscape News turned in a very positive assessment not only of the Alter study
but the impact of the study on the field. We learned that the Alter group tested
some of the CDC’s samples but that they weren’t able to provide samples to the
CDC themselves because they didn’t have enough material.
Dr. Alter suggested that the different retroviruses the WPI and his group picked up
may be due to geographic differences in prevalence and patient selection.
“Dr. Alter said the most likely reason for the discrepancy in results is patient selection. Diagnosis of CFS is based on a symptom complex, not a specific disease marker.
All patients in the NIH-FDA study met the accepted diagnostic criteria for the syndrome, and most blood samples
were from the patient population of a single coauthor, who is a CFS expert, he said.
“There may be a geographic difference,” Dr. Alter told Medscape Medical News.
“In the Northeast, CFS may be due to MLV, and in the West, it may be due to XMRV.”
which is an interesting idea but doesn’t seem likely, at least from this
laymen’s perspective, to hold.
It’s true that the WPI patients came from
doctors across the country, none of which to my knowledge, was in the
Northeast. The WPI, however, has found XMRV variants in those patients dating back to the original paper. While those variants were not in the
original paper they were used as supporting material for the Science editors who
wanted confirmation that the WPI was not looking at a contaminant. The bottom
line is that the WPI has apparently known of XMRV variants from the beginning.
Eleanor Stein at the University of Alberta is starting an XMRV study for people
living in Calgary and Edmonton.
Interested Calgarians are asked to call
403-287-9941 and Edmontonians 780-492-8415. Article in Calgary Sun:
Alter paper and found alot that it liked. Stating that “Even skeptics are impressed
by how much care the authors of the new study took to ensure accuracy” it was
clearly a very solid piece of work – even Dr. Monroe of the CDC agreed to that “The data do seem solid”, admits Steve Monroe, director of CDC’s Division of High-Consequence
Pathogens and Pathology.” And he wasn’t the only one “It’s simply a good paper,” adds virologist
Reinhard Kurth, former director of the Robert Koch Institute in Berlin.
Alter, a widely respected virologist and winner of the Albert Lasker Award for Clinical Medical Research,
“clearly knows what he is doing.”
Questions lingered about reconciling the ‘new’ retroviruses found and the inability to find XMRV, and the disparate results of the other studies, and clearly more work needs to
be done to get the scientific community as a whole gets on board but one had the
feeling, barring some untoward surprise, that that was a matter of time. With regard to those ‘new’ retroviruses, Dr. Mikovits
reported that the WPI, over time, has found new variants. (In fact, Dr. Mikovits told me they are present in the WPI’s patent
When will the research community get on board – one way or the other? We finally got
what appeared to be a solid date: “By
Christmas”, Dr. Kurth reported – by Christmas they will have come to a consensus.
– BeesKnees on the
Forums reported that the the National Cancer Institute and Science Applications
International Corporation (SAIC) are creating an XMRV Toolkit to help study the
virus. We heard that the NCI had spent over a million dollars on basic XMRV
research and this may be the fruits of their labor. This toolkit, which consists
of ‘expression plasmids’ for all the proteins in XMR, will assist researchers in
many ways; developing antibody test, as a diagnostic tools, developing
vaccines and immunotherapy. It should accelerate research
greatly…..“The development of these
XMRV tools is expected to save researchers months in laboratory
production time and thousands of dollars in labor costs.”
The development of this tool demonstrates the leadership role the NCI
has played in XMRV. It also starkly illustrates how hands off the big retroviral institute at the NIH, the National Institute of Allergy and
Infectious Diseases (NIAID) has been. Patients and some researchers have been critical of the CDC’s XMRV study but we should all
take note of the fact that if it was up to the NIAID, there might be no research at all
on XMRV. At least the CDC
has devoted some time and money to this issue. The NIAID backed away from ME/CFS
long ago and it continues to treat it as it would a pariah disorder. One might
ask who the bigger ogre is in this scenario.
– The FAQ’s suggest that both the CDC and Dr. Alter are testing each others
samples. Dr. Alter did not find XMRV in the CDC samples either but what about
those MLV? And what had the CDC found in Dr. Alter’s samples? All questions we
hope will be answered in that increasingly exciting Sept workshop.
– It took them, what? At least
six months, but the CDC has finally put the job posting for the CFS job out but
the timing or this is terrible and it suggests that either they’ve decided about
the role XMRV plays in CFS or they just don’t care. With scientific consensus on
this all important pathogen just a few months away why not wait and be sure to
attract the right kind of individual for the job? The posting opened Aug 19th
and closes two weeks after that.
- Four Viruses? The Alter Paper Arrives: A Review – I just posted a long review of this
complex and fascinating paper, and what, so far as I can figure out, it means.
DeMeirleir Reports RedLabs and Researchers Confirm WPI Findings – Dr.
DeMeirleir reported XMRV was alive and well in European ME/CFS patients. Unless
they are using a different technology than that licensed to them by VIP Dx this
was welcome but not startling news, as few expected the virus not to be found in
Europle. The most intriguing part of Dr. DeMeirleir’s accouncement was that he
had identified an immune signature similar to that found in ‘symptomatic’ HIV
patients. There was no telling why that signature had not popped out before in
ME/CFS but it could be that it is showing up now because of the more
selective cohort (ie XMRV positive patients). Dr. De Meirleir sounded very
hopefull stating “It seems that for the roughly 17 million CFS / ME patients
world-wide end to a long ordeal surrounding the recognition of their illness.
The development of targeted therapies is already underway, both in Belgium and
abroad” He will report his finding at the Sept 7/8 workshop.
Media Coverage of the Alter paper, as expected, rapidly followed. For
check out here
- Business Week
New York Times
- Wall Street Journal
- New Scientist
- Kitei Paper on Alter Story – doing her due diligence Mindy Kitei at CFS
Central not only got a hold of the paper before publication but also interview
Dr. Alter, Dr. Komaroff and others. (You
can now find the paper here.
Check out a commentary on the findings here)
The surprise of the paper was what Dr. Alter didn’t find – “XMRV”! Even more surprising was the fact that
his finding of a melange of closely related viruses actually made sense in some ways. One reason that none of the six or so
CFS studies have been able to find ‘XMRV’ may be that the type of XMRV they looked for was different.
As Dr. Mikovits reported in
“A Different Kind of XMRV” the reference type for XMRV testing was
derived, naturally, from the sample they had on hand which were from prostate
cancer patients. Several studies since the publication of the Science paper have
indicated, however, that the makeup of XMRV in prostate cancer tissues
very likely differs from that found in the blood cells. That appeared to be due
to the APOBEC3 enzyme present in blood cells which swapped out amino acids in
the RNA of the virus.
Dr. Mikovits talks about this is a
video posted shortly after the finding,
where she states that it appears that ‘a family of murine retroviruses appear to
have infected people with ME/CFS.
It’s still a mystery, at least to me, however, how the WPI
found XMRV at all since they presumably started searching for it in the blood last year using
the material they had on hand -which were reference samples from the prostate. It may be
that faulty methodology indeed, still does play a role in the inability of other
groups to find this virus.
Kitei rKitei reported
that Dr. Alter believes his
findings confirm the original XMRV findings stating “Viruses tend not to be homogenous,� Alter explained to CFS Central
in a telephone interview. �The fact that we didn�t find XMRV doesn�t bother me because we already knew that retroviruses
tend to be variable. They mutate a lot, basically. This is true of HIV and HCV [hepatitis C virus]. It�s not one virus. It�s a family of viruses.�
Dr. Alter should certainly know – his work on hepatitis viruses that lead to the discovery of two new
viruses garnered him the ‘Nobel Prize’ of Medicine – the Lasker Award.
Dr. Alter found no less than four different types of heretofore undiscovered mLV’s in CFS. They were named, appropriately,
“CFS Type I”, “CFS Type II”, etc.
Mutating over time like any good virus should – Dr. Alter was also able to find the pathogens in blood that was fifteen years old
and then retest those individuals today. He found the virus present in 7/8 of them in mutated form – which is exactly what one would
expect from a virus over tiem.
According to Kitei, Dr. Alter felt the delay in releasing the study
only strengthened the study, stating �There were no changes in the conclusions,
but we added data that made the conclusions stronger,� he explained. �For one
thing, we did some further work to feel confidant that there was no
contamination�. We had hundreds of negative controls, and every assay had
negative controls. And then we used an assay from mouse mitochondrial DNA and
found that there was no evidence of mouse contamination. We had variation in the
viruses we were finding. If there was a contaminant, you�d find one species, not
Now Dr. Alter will give XMRV its next big test – he will search for it in a wide variety of
disorders. The danger is that it is widespread in chronic diseases, which, would negate its importance
unless it really is some sort of superbug. Hopefully, it will be found clustered in a series of
‘NEID’s’ such as FM, GWS, MCS, IBS. Now we await the results of the briefing.
For more on Mindy’s
- CFIDS Associations’s Take on the Finding
- Alter Paper Released Today at 3:00 pm EDT- Telebriefing Follows – From the
Telebriefing by experts from the Food and Drug Administration, the National Institutes of Health and the Centers for Disease Control and Prevention to respond to questions about this study. The paper is currently under embargo until Monday, August 23 at 3:00 p.m., by the Proceedings of the National Academy of Sciences.
- Harvey Alter, M.D., Chief, Clinical Studies and Associate Director for Research, Department of Transfusion Medicine, NIH Clinical Center
- Shyh-Ching Lo, M.D., Ph.D., Director, Tissue Safety Laboratory Program, Division of Cellular and Gene Therapies and Division of Human Tissues, Office of Cellular, Tissue and Gene Therapies, Food and Drug Administration Food and Drug Administration
- Celia Witten, M.D., Ph.D., Director, Office of Cellular, Tissue and Gene Therapies, Food and Drug Administration
- Hira Nakhasi, Ph.D., Director, Division of Emerging and Transfusion Transmitted Diseases, Office of Blood Research and Review, Food and Drug Administration
- Steve Monroe, Ph.D., Director, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention
Monday, August 23, 3:01 p.m. EDT
How: The initial briefing will be for press only. The NIH has informed us that the briefing
should be available to everyone on replay approximately two hours after briefing concludes. For replay, dial 1-866-373-4990 and enter passcode 5711.
- VIP Dx Announces New Tests – In a nice bit of timing
VIP Dx announced a new antibody test for
XMRV and its related variants. The related variants item – the fact that
more types of human murine related retroviruses are present in ME/CFS- is the
second bit of big news we expect the Alter paper to bring. This finding – that a
variety of heretofore undetected ‘mouse’ retroviruses, all closely related to
XMRV have infected the human population could, one would imagine, unleash an
enormous amount of interest in the scientific community and possibly pave the
way for insights into a number of different diseases and/or explain the
different subsets in CFS. (If 80% of CFS patients test positive for XMRV then
something will need to explain the subsets within that
subset). The case with HIV is possibly quite instructive as different
types of HIV result in dramatically difference illness courses with the
mortality rate for one form significantly lower than the other.
Special Edition of CFIDSLink on XMRV Announcment Due This Afternoon
- Dr. Peterson on XMRV, Ampligen, antiretrovirals, stem cells and more
– Check out this very interesting review by mJoey on the Phoenix Rising Forums
of his latest meeting with Dr. Peterson….mJoey got deep into the some
important issues with the Doctor who’s been at the center
of it all.
- The WPI Opening Ceremony speeches – check out
(and very professional) speech and Andrea’s very moving speech. When you
Andrea’s speech look at how strong and assured she looks. When I was at the
Awards Dinner at the Reno Conference last year in March I was told she was there
with her doctor because of her severe seizures…she has clearly improved
dramatically. The research center of the WPI is now named the Mikovits Research
- Alter Buzz – the Buzz around town is that the Alter paper is coming
out this week and that it will completely confirm the WPI’s findings and
go further. That, in fact, is what we would expect
– each paper should build on the other ones and go further. If the Buzz is
correct the blockbuster paper will come out on Tues. Only time will tell; if it
is don’t be surprised if you
see articles in the media appearing the same day. (In fact they may come out
first if you’re up early enough).
- Opening the Door to a New Era: the WPI Arrives
– check out an article I wrote looking
at what Annette and Harvey Whittemore have accomplished and celebrating the opening of the WPI.
State of the Art Facility’ – That was how Dr. Barsky described the 77
million dollar Center for Molecular Medicine which the WPI is housed (along with two other programs). The Whittemore’s kicked in a cool $5 million
dollars of their own money to get the facility built. There’s quite a bit on the WPI on this nice overview
of the new building. Check it out here.
- XMRV in Press — papers
on XMRV continue to pour out. The latest, a 50 plus page tome, described
successful efforts to detect antibodies in XMRV infected primates. Interestingly
they reported XMRV illicits a ‘much less robust’ antibody than HIV. Initial
antibody levels are high and then decline quickly to basal levels (?) after
about 4 months. They believe this is probably due to reduced replication levels
as the body gets the infection under control although they did note another
study indicated the virus was present in many organs (even if it’s not
replicating). A similar antibody response occurs in HTLV infected primates
and it may not reflect what happens in humans.
Dr Katz on XMRV, the Big Study, the Elephant in the Room and What the Heck CFS
is – if you missed the CAA’s webinar on blood issues it turned out to be a
very good one with Dr. Katz being an engaging speaker who’s had a long-time
interest in CFS.
Check out an overview here.
- HGRV Debuts
– A name change already? Now that is something people with
ME/CFS/CFIDS/ME/CFS/EBV Syndrome are familiar with. Things are moving fast at
the WPI. Feeling confident that issues about the XMRV’s existence have been
settled they are building a foundation for the future, part of which involves calling this
pathogen by an appropriate name. As Dr. Burrascano pointed out XMRV is a human
not a mouse (ditch the M), you can’t say its an exogenous virus because
it’s a uniquely human virus (scratch the x); what it is is a human infectious gamma
retrovirus – the first one we know of; ie its an
HGRV…..the pronunciation of which is up to you. (These are biologists not poets). From an aesthetic standpoint it only
gets worse…the disorders associated with HGRV are HGRADS (Human gamma retrovirus associated disease).
So, congratulations – if you tested postive for XMRV you may have an HGRAD.
The tongue twisting names are not, unsurprisingly, going over well at the Forums. One person suggested it sounded like a
rocket launcher from the Soviet Union.
Some Forum members
have jumped in with their proposals. Human Associated Gamma Retrovirus Disease or HAGRID gets the
Harry Pottery character into the picture while being more picturesqe – I feel Hagrid – (haggard), HGIV, HGRV,
That the new names will be proposed
in a just a few weeks at the XMRV Workshop on Sept 7th – demonstrates again how
confident the group is and suggests they may believe enough positive information
will be coming out over the next couple of weeks to sway the group. What a turnaround this is from a couple
of weeks ago when the CDC, having locked up the Assay presentation at the workshop, appeared to be in drivers seat with XMRV.
Hold onto your seats, Dr. Burrascano, a member of the Symposium stated “the volume of new and important information about this virus and its disease associations is increasing rapidly”.
The Lo-CFS Connection – Dr. Alter appeared out of the blue; a major
researcher without any apparent connections to ME/CFS he appears to have stepped
in at just the right time to, kind of, save the day. But is he really out of the
blue? A thread on the Phoenix Rising Forums indicates that his partner,
Dr. Lo, played a major role in mycoplasma research and actually authored a paper
on CFS and mycoplasma. His record suggests that he’s very good at finding
difficult to find bugs. He did not find an association between mycoplasma’s and
CFS but it may be that he thought at some point a bug was going to show up.
- Dr. Mikovits
Breaks the News on the FDA Paper
-Several weeks prior to publication Dr. Mikovits spilled the beans on the
FDA XMRV paper,
stating in an interview with RGJ.Com, what has seemed to
be more and more obvious – that the Alter paper is going to confirm the WPI’s
findings when it is released. While no one yet had directly said so, the news
seemed to be in the air. In an interview in Nevada Newsmaker Annette Whittemore
very confidently said several new replication studies will shortly out confirm
the WPI’s findings and the mood overall seemed very good.
It’s a big day, a huge day for CFS and, of
course the WPI. How fitting that the WPI, which has endured six months of
skepticismas study after study has
failed to find XMRV not only in ME/CFS but in other diseases, was greeted with
this news as they cut the ribbons on their new facility. While much work remains
to be done the news that the several positive studies are on the way potentially
means a new dawn for ME/CFS. The
implications of the finding are truly immense – legitimacy, vastly increased
funding, new treatment possibilities and an immense, immense weight taken off
ME/CFS patients shoulders.There was already good news on the treatment front from Andrea Whittemore, who
had became dangerously ill after having to go off Ampligen, as
reported on Nevada Newsmakers that she had improved significantly on new
treatments linked to XMRV. With the confirmation of XMRV in CFS the drug
companies appear to be picking up track right where they left off six months ago
when the negative studies appeared. Dr. Lombardi stated that treatment trials
could begin at the WPI soon.
Representatives of drug companies and diagnostic laboratories are reportedly
among those attending the WPI’s Symposium this week.
Annette reported that the the WPI is
putting together a team of physicians to lead the medical end of the WPI as fast
they can and hope to open in medical side of the facility in late Fall.Dr. Mikovits also scooped herself on a paper she expected to published at the
end of this year that she reported will demonstrate distinct immune
abnormalities are present in ME/CFS patients infected with XMRV. This is a major
accomplishment because it suggests an XMRV infection could have profound effects
on the immune system indicating it is more than a ‘passenger virus’. With
researchers able to show XMRV is causing distinct immune abnormalities the next
step is to show that drugs that remove the virus and recorrect the immune system
abnormalities lead to improved health. Three drugs have been able to stop XMRV
in the lab and Dr. Lombardi felt many more were potential candidates stating
there was alot of ‘low-hanging fruit’ available on drug company shelves.