XMRV – Puppet Master?

October 15, 2009

Posted by Cort Johnson

The idea that  XMRV could be a kind of ‘puppet master’  (eg. Dr. Bell) that allows other infections such as EBV or HHV6 or Lyme or enterovirus to  become exacerbated is generating discussion.  Dr. Coffin suggested such in his article “A New Virus For Old Diseases”. Dr. Huber, a researcher studying endogenous viral elements in ME/CFS has suggested that XMRV might be able to unlock endogenous retroviral elements in our DNA.  Based on the limited results from his clinic Dr. Cheney speculated XMRV could be a factor in autism and ADHD and (wondered about arthrits, asthma and cancer!).  Dr. Mikovits has reported that XMRV can be found in autism and ‘atypical MS’ patients. Its all a bit overwhelming.

Autism - The Nevada Autism Commission revealed that 40% of a ‘small group of children’  with autism tested postive for XMRV.  Dr. Mikovits verified this stating ” we have actually done some of these studies (in ASD children) and found the virus in a significant number of samples that we have tested for. It could be linked to a number of neuro-immune diseases, including autism” but that at best it would be one  several factor that contributed to the disorder.  Dr. Mikovits also speculated that the virus could be a factor in  vaccination triggered autism.

Infectious mononucleosis – No one’s mentioned a key factor in many patients journey  – infectious mononucleosis.   Could an XMRV infection be a risk factor for getting infectious mononucleosis; ie. do people who get the more severe form of Epstein-Barr virus infection (infectious mononucleosis) rather than the  less severe form (mild cold)  tend to carry the XMRV virus?

When the Dubbo and  Taylor  groups dig into their samples they could show that XMRV is not restricted to the ME/CFS patients. It turns out that if you have infectious mononucleosis you also have an increased risk of coming down with multiple sclerosis and the WPI has already reported finding XMRV in ‘atypical’ MS patients. Could the scenario go – XMRV infection in childhood = increased risk of infectious mononucleosis = increased risk of ME/CFS or multiple sclerosis.

Other Diseases – ME/CFS is not the only disease with disabling fatigue, cognition problems, sleep problems, etc. Besides related diseases like fibromyalgia there are also a number of diseases which don’t appear to be related to chronic fatigue syndrome at all but which have subsets of patients who look very much like chronic fatigue syndrome patients.  A significant subset of post-cancer patients, post ICU patients, post heart surgery patients, patients with liver disease and multiple sclerosis patients have a very CFS-like condition. Researchers have speculated that they are in fact chronic fatigue syndrome showing up in other diseases.

Still a Stress Trigger? What these conditions share is a stress trigger; whether it comes in the form of an infection, a physical trauma ( fibromyalgia), cancer treatment, surgery, etc.  This, of course that the stress response plays a critical role in the development of this illness. Note that this does not at all conflict with any of the statements that Dr. Mikovits has made regarding possible triggers for XMRV activation; two of them she mentioned – cortisol and inflammatory cytokine levels  – are increased during the stress response. Could the CFS-like post-cancer, post-ICU,  MS patients, etc. patients be harboring the XMRV virus? The possibilites for this virus – at this very early stage when we don’t know much – appear to go on and on.

Why might retroviruses at least theoretically be able to trigger so much disturbance?  Because we’re pretty much stuck with them; instead of eventually getting killed off in the body like other viruses they tend to linger in the body  – i.e. they are chronic – and  they can be pretty good (aka HIV) at creating a condition which other pathogens can take advantage of.

Let’s not forget , though, that most retroviruses are completely harmless. In fact our DNA is studded with the remnants of old retroviruses that have embedded themselves in our genome. Before we can get too excited we need evidence that this retrovirus is tied to the symptoms in chronic fatigue syndrome; i.e. the more retrovirus you have the sicker you are.

Dissenting Views - There is also some reason to believe that this virus might not be some sort of ‘Puppet Master’ that turns on a ‘viral cascade’ in patients. A study by Dr. Nicholson found that one virus does not appear to open the door to another virus in ME/CFS patients. Instead ME/CFS patients as a group tend to harbor one or another opportunistic viruses.  Dr. Natelson reports finding very, very few viruses in the patients that he sees.

Reports from the WPI, on the other hand, mention finding dozens of  different types of viral fragments in the sophisticated tests in chronic fatigue syndrome patients and very few in controls. Is technology the difference here? Or are these physicians looking at different types of patients? Clearly we’re still in the early stages of getting a clear picture of the viral component in this disorder.

The XMRV /XAND Pages On Phoenix Rising

16 comments

{ 16 comments… read them below or add one }

John October 16, 2009 at 12:46 am

Yeah this whole thing is so cool but kind of exasperating as well, at least for me with my gradual onset, no sore throat/no swollen lymph node, thyroiditis-having but thyroid hormone intolerant(which basically precludes my participating in CFS research studies), 6 weeks solid of post-exertional malaise having, thirsty all the time with a progressive disease course illness!

One thing that kind of made me feel better were the unpublished reports of 95% antibody levels among other patients- they didn’t mention anything about requiring sudden-onset cases, but then again they didn’t mention anything about sudden vs. gradual in the Science paper either. But if XMRV were implicated in more than the sudden onset cases, Jesus Jumping Jehovahfat, can you imagine all the research money? From 5 million in ’08 to 4 million in ’09 to 3 million(projected) in 2010, to what- tens of millions, more likely hundreds of millions every year?

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Roy Snow October 16, 2009 at 4:07 am

The WPI has renewed the hopes of our community. No matter how this new research works out, the folks that set it up have shown wisdom and determination that will obviously continue and grow. The Whittemores could have just donated their large sums of money to the big CFS group. The fact that they didn’t speaks volumes.

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cort October 16, 2009 at 6:16 am

I’m with you their John. I have gradual onset, no evidence of pathogens except some stomach bugs, low cortisol, zero growth hormone, some spinal fluid abnormalities, lots of sore throats but no EBV, HHV-6 etc. We really need to know who they’re testing.

Research on the immune system should increase dramatically though it’ll only be temporary if this thing doesn’t get replicated. The NEXT study is the most important one.

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Erik Johnson October 16, 2009 at 4:00 pm

The testing was on the original cohort, used as prototypes for CFS in the 1988 Holmes committee study group.
Which means that this is the specific phenomenon that “CFS” was commissioned to investigate.

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cort October 16, 2009 at 5:08 pm

Good point Eric! I came to much the same conclusion. Which is what makes me – personally – a bit worried – and lead to the next post: XMRV- Hope and Caution –
http://aboutmecfs.org/blog/?p=969

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Elsie Owings October 18, 2009 at 4:24 am

Some of the previous viral tests have reflected only momentary disease states: positive for a virus one time; negative the next; then positive again … if you were able to get the tests done repeatedly. Even the low NK cell cytotoxicity rates that Dr. Klimas tests for have a tendency to vary( if I recall correctly) according to the patient’s condition at the moment. I tested abnormal on that test, but then again, I also was just recovering from a cold at the time, which might have influenced the results. I’m not entirely confident that the test would come out the same if I had it done again.
I guess the bottom line is that most of us have been told so many times that our test results are “normal,” that we’re more than a little scared to believe that it’ll be any different this time.

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Elsie Owings October 18, 2009 at 4:45 am

Regarding the research funding issue, I’m a bit too battle-scarred from previous advocacy attempts to expect much in that area, either. Dr. Klimas is correct that follow-up studies need to be conducted VERY carefully so as not to allow “sloppy science” to provide room for dismissal of the results. But even if the results can’t be dismissed, they can be ignored, and that has been the case in the past. This is not the first time that impressive findings have come up in CFS research: there’s been the RNase-L enzyme, abnormal NK cell functions, etc., yet our governmental agencies have still managed to turn a deaf ear. Every time a new study comes up, the CDC makes a public statement that this is a “real” disease, and then as soon as the hoopla dies down, they go back to cutting our funding and psychologizing our disease. Amazingly, they did this even after Reeves’s own pet project, the genomic and proteomic studies, showed abnormal results. No matter how abnormal the test results are, governmental funding will only pursue the directions that its leaders set for it. That’s why I’m so grateful for the WPI and the few other dedicated research centers who somehow manage to continue the research even if they don’t get a great deal of government funding. It will probably be up to us to make sure that these organizations continue to receive adequate funding. I also hope to find out which labs will be doing follow-up studies on the XMRV, so that I can either do some fundraising, or become a participant in the study, or both.

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Jean Harrison October 18, 2009 at 8:33 am

A couple of things. As this seems blood born hemopheliacs could have a high rate of ME-CFS (though perhaps patients were too ill to donate blood).

Also I read that the WPI used the Canadian Criteria. Terrific news. In order to replicate, other teams have to use the same criteria for their patients – to be rigorous. Also this finally gets the Canadian Criteria into publication, so it can /should/will be used in future publications..

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Anita Burgess October 18, 2009 at 10:23 am

Cort, To answer some of your ponderings. Infectious Mononucleosis is caused by the Epstein-Barr Virus. About 90% of the population get mono in their late teens and early 20s. Some have such a mild case they dont even know they had it. Others get sick for 6wks or longer. The EBV then lies dormant in their body unless some other immune problems (ie another illness or virus) comes along and it is reactivated. Many if not most PWC-MEs will have reactivated EBV from time to time. It just lasts a lot longer than the typical 6wks of mono. And the patients, already very ill from ME/CFS will just be sicker with the “Reactivated” EBV. EBV also causes Lymphoma. “Atypical MS” is NOT a form of MS! MS comes in different forms but “Atypical” is not one of them. The only time I have seen “atypical MS” is in referring to ME/CFS because our symptoms are so similar to MS. I am very excited and hopeful for the future of XAND.

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Melissa Badley October 18, 2009 at 10:48 am

I am a relatively new person to this blog, and to all of the research about ME/CFS – (primarily just the last 2 years.) My illness has so long – and until I finally had to quit working entirely, I had only the energy to drug to part-time work and come home to ‘drop”. My sanity is maintained by keeping up – as much as I can – with what is happening in research now. I am new to the details of the controversy, but aware of it through the devastation I have experienced in my search for good medical care and understanding.

I am also, very hopeful that research will not only be carefully completed, but verify connections of a causal agent and/or a way to validate our illness. The destruction of this illness to us physically, and financially, and finally to our personal relationships is simply devastating. My case is a “mild” case, with little to no verification from the medical community – eventhough I haven’t lived a full or productive life for 16 years.

While I wait for validation, I also hope for a cure. It is a race against time! One that for me would be helped greatly at first with at least a means to prove that I am ill to others. I know something caused my immune system to become dysfunctional. I just wish I could prove it to everyone else, including my family, friends, and most importantly the medical community in which I’ve lived!

I give all my heartfelt prayers and wishes for the WPI and collaborative researchers who who are workfing to find answers for us! I hope the pieces really do begin to fit together and efective treatments are swiftly found! I hope we don’t linger around for another 10-15-20-30 years!

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cort October 18, 2009 at 12:03 pm

“A supernova (pl. supernovae) is a stellar explosion. Supernovae are extremely luminous and cause a burst of radiation that often briefly outshines an entire galaxy”

This discovery has the potential for being a world changing event in every way for us. Its like a supernova hitting this community – except with staying power. The illumination it provides would redefine how this disease is viewed. If it works out (cross your fingers tightly!) we have validation, a specific focus for research, and abundant funding.

Lets take a look at the second item – a specific focus. The lack of ‘something specific’ to focus on – a single injury or site of damage or pathogen or a biomarker – has been haunting us for 25 years. For 25 years the research community has ignored the damage and devastation caused by this disease because this disorder could be tied up with a yellow ribbon and fit in the right box.

Essentially chronic fatigue syndrome always been too messy of a disease – too many interlocking parts, too many parameters, too many symptoms (!) – for our finicky right brain dominated research community to bother itself with. Their technology may have grow exponentially in complexity but their mindset of the research community has remained darn primitive.

They don’t want complexity – they want ‘it’. Once they have ‘it’ they’re very good at taking it apart, changing it, putting it back together and if necessary, finding a way to kill it. But if they don’t have ‘it’ they’re at a loss; basically they don’t know where to begin – so for the most part, they don’t, they just push it to the side and focus on something else. You can talk about all your conspiracy theories or all the neglect but that’s it in a nutshell; because the research company never had a good toehold on this disease they pushed it off to the side.

But now they may have ‘IT” and that changes everything.

Its not that there haven’t been advances. There had been plenty of advances in this field but they’ve all been somewhat problematic. For instance MRI readings have shown areas of abnormalities exist in ME/CFS patients brains for several decades. That’s great! Except those injuries are in different places of the brain different patients and that knocked that area of endeavor dead in the scientific community.

Ditto with herpesviruses; researchers can find herpes virus activation in some patients but not all, there are a range of herpesviruses, people can have herpesvirus activation and not get sick, opinions differ on the right diagnostic test – there’s still alot to tidy up in the herpesvirus world. What do you get when you add a ‘messy’ field of research to a messy disease? The cold shoulder from the powers that be.

Researchers have also been able to find pretty consistent abnormalities in heart rate variability, natural killer cell dysfunction, RNase L dysfunction, oxidative stress and some others but none (amazingly to the patient community) appear to have the slightest difference to the scientific community as a whole. All of these though, have their little ‘problems’; the scientific community is still not sure how to assess HRV or RNase L dysfunction (its too new and is only associated with chronic fatigue syndrome), oxidative stress is common in chronic diseases and probably because natural killer cells aren’t T cells they don’t seem too excited about natural killer cell dysfunction. Naysayers can (and have) explained away the significance of virtually all of those. None of them are potential ‘Game Changers”.

But a pathogen…..a pathogen is different. Researchers have been studying pathogens since modern medical science begin. Popular books are written about ‘Pathogen Hunters”. People win Nobel prizes for discovering pathogens. Pathogens get the juices of the scientific community going. They make careers. They’re probably the sexiest topic in all of medicine.

Plus although viruses may be vanishingly small bits of RNA or DNA they’re infinitely easier to study and understand than ‘multi-systemic’ disorders. The research community is just beginning (belatedly) to develop the tools and protocols to assess how the systems interact with each other but they know how to study pathogens.

So what could happen if this really works out? That’s ‘works out’ as in this virus is shown to cause the majority of chronic fatigue syndrome patients disease and possibly other diseases as well?

We start to leverage the assets of a huge cadre of pathogen researchers. (If this works out you probably won’t even recognize the names of the researchers writing papers on chronic fatigue syndrome (or XAND or whatever its called) in several years.

Funding explodes – Studies have shown that this disease causes 25% of those affected to go on disability. It costs families about $20,000 a year. It costs the nation about $20 billion dollars a year in economic losses! That’s a lot of money even for a disease. Yet this disease is ranked about 210th in rank of the 215 diseases and conditions in NIH funding. It receives about 3 million dollars a year from the NIH in funding.

Three million dollars a year is never going to solve any disease -its chicken feed, chump change the NIH throws to keep the beggars quiet. Three million dollars is a rounding error for AIDs funding. Ten million dollars – three times the current level – is peanuts and hardly worthy of mention.

Asthma causes much lower economic losses tha ME/CFS yet gets almost $300 million dollars a year in federal funding. Once this disease is validated think hundreds of millions of dollars A YEAR in funding once the field gets built up. That’s more funding in one year than this disease has gotten in twenty.

The little CFS program that’s been slowly sinking in the backwater of the Office of Research Of Women’s Research (ORWH) where its received no funding (that’s no funding!) gets moved back into the mighty billion dollar National Institute of Allergy and Infectious Diseases (NIAID) where researchers will fall over themselves trying to hook into the next big thing.

Things change at the CDC. It’s hard to imagine that the CDC would keep around a virologist (Dr. Reeves) who not only missed the biggest virology in several decades but seemed to have little interest in anything viral in this disorder. Let’s not forget the hot virologists at the CDC who would probably begin clamoring for his position. Who wouldn’t want to lead the lab that might unlock the mysteries not only to chronic fatigue syndrome but to fibromyalgia, autism and other disorders.

Everything we’ve wanted as a group; validation, recognition, funding – it all gets solved.

Right now it’s all a bit pie in the sky but while the WPI has been mostly circumspect in their public announcements the word behind the scenes is that they’re very confident in their findings. Did we just get hit by a supernova? Did our world just change for good?

The possibilities are simply extraordinary.

(this has turned into a blog! Gotta move it up there!)

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meghan Shannon October 18, 2009 at 1:11 pm

Hi Esie, Anita and Jean, Great to see we are all still around for this.
I know this is a bit overwhelming, however the truth is we have all known that we are sicker then “a dumbass name” CFS (quote from CFS Blues song AACFS 2004)

Also Dr. Klimas has said for 15 years “There is a reason HIV-AIDS doctors are seeing CFS/CFIDS patients in the USA”
Dr. Oleski on the CFSAC board is one from New Jersey, Dr. allen McCutchen saw me and many others and there are many more HIV-AIDS doctors who have followed us and stuck with us.

Dr. Elaine DeFrietas in her Congressional testimony with Dr. H. Krowpwoske from Wistar Institute even said, “this is not about fatigue…in fact some researchers are saying this is Acquired Immune Defiency Syndrome NON HIV”. I have a copy of her testimony from April 1991, if anyone wants it.

meghan Shannon

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drew October 18, 2009 at 4:30 pm

Cort, your comment above (the supernova comment that “turned into a blog”) brilliantly captures just how significant this finding may be. I’m getting very excited, although I know we have to proceed with caution here!!

Drew

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John October 27, 2009 at 10:07 am

Ok, what follows is an effort to form a train of thought about some potential pathophysiology of XMRV infection. Any and everything below could be absolutely and completely misinterpreted and/or mistaken.

All aboard!

So I think I remember seeing a quote of one of the researchers, possibly Dr. Mikovits, saying something to the effect of XMRV might cause red blood cells to have a reduced capacity to carry oxygen.

If the blood can’t carry enough oxygen, then the autonomic nervous system would be put on overdrive, wouldn’t it? I actually don’t know autonomic from sympathetic, so sorry for mixed up terms. Anyways I know for myself that when I exert myself my heart will go on beating for a really long time, like hours. Even from just a bit of exertion my heart will still be pounding fast 30-45 minutes later.

It would also cause the blood vessels to expand, wouldn’t it? To get oxygen to the muscles? And blood vessels expanding would cause low blood pressure? Because it doesn’t seem like the body would produce more blood as a result of a person’s blood vessels expanding because if they got the oxygen they needed and constricted things could get ugly. Anyways, so the blood vessels would expand and this would cause blood to pool in the gut, legs, etc. because there wouldn’t be enough bp to get it to the brain. What you end up with is decreased oxygenation of the brain, decreased tolerance to exercise, anything else?

So that’s one hypothetical pathophysiology for XMRV. What would cause blood vessels to constrict like the Incline Village/epidemic patients are reported to have happen? People losing their fingerprints, etc? (sorry if this post is loopy, it’s getting to be time to go to bed)

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ForYourInfo December 22, 2009 at 3:52 pm

WPI did not stack the deck. My son was invited into the study with no blood work at all. He was asked by the company who had done a previous study on my son. They were not given that blood work as it was the work of someone else and their study on something completely different. He as asked in because he has Autism and I was told about the study and called and said I would love to be in this. No one knew anything but that he had Autism. If you could see my childs blood work he looks like an Aids Paitent but that was done long after I had done this study and they do not have copies of it at all. My Neuro could not give out his blood work anyway without my consent but being as the Neuro just ran all his blood work and this blood was take about 6 months ago they had no clue. So the guessing that everything is stacked in the testing is Bogus!!!

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admin December 22, 2009 at 5:37 pm

If your son had autism he did not participate in the chronic fatigue syndrome study – that was a different ‘study’ he participated in. There’s nothing the matter with ‘stacking the deck’; its how research is generally done with a first study – you put your best foot forward; ie use the patient group most likely to prove your case – probably your most severely ill patients. After you get your foot in your door then studies start looking at more representative patients.

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