The IACFS/ME did a very interesting thing by inviting Dr. Mikovits to answer questions from their members. Dr. Mikovits must have known she was going to get some tough questions and she did.
The Tricky Immune System - The first question illuminated what a complex process tinkering with the immune system is. Andrew Bokelman essentially asked -if you give CFS patients something (such as a neutraceutical) that activates the immune system – causing natural killer cells to increase – if those natural killer cells are infected, as has been reported, with XMRV, aren’t you just spreading the XMRV infection?
With every answer we learned a little bit more about XMRV. Dr. Mikovits noted the critical fact that while XMRV may be present in many cells it doesn’t appear to be very active in many cells. (We’ve heard before that XMRV does not appear to be very active in many immune cells – which, of course, brings up the question -just where is it active? ie. what is its tissue reservoir? and what effect, if any does it have on immune cells?). In any case, Dr. Mikovits stated that we don’t have to worry about empowering XMRV when we enhance NK cells; the WPI has been able to enhance NK cell killing levels without increasing XMRV replication.
Sex and XMRV - Dr. John Chia asked how XMRV could be transmissible via blood, sex and body fluid as stated in ‘the newspaper article’ – when there is little epidemiological evidence of infectious transmission in CFS. He noted that long before HIV was determined to be the cause of AIDS it was pretty clear that sexual transmission was involved; researchers were able to chart the transmission of HIV from person-to-person simply by following their sexual partners. This is clearly not true in ME/CFS.
Dr. Mikovits stated that sexual, blood and body fluid transmission was only suggested by the Science paper and that newspapers went too far in stating that it occurred. She then noted, though, that unpublished work indicated that XMRV was ‘very stable’ (ie it can survive in many different environments) and appears to be very ‘transmissible’; ie it does indeed appear to be transmissible via the blood, sex and body fluids.
She didn’t answer, why, if this is so, CFS itself does not appear to infectious in nature (ie does not generally occur in outbreaks – and is not usually transferred between say, a husband and wife.) Of course just because XMRV is easily transmissible does not mean that everybody who has it will get sick. It could be quite prevalent in families of ME/CFS patients but does not manifest itself in most people as CFS. The WPI is testing families of ME/CFS patients now.
Posting a Ride on the Immune System – A few questions ago we learned that enhancing natural killer cell activites does not, at the same time, help XMRV spread through the body. In her answer to a question on the effectiveness of new biotech drugs for XMRV, Dr. Mikovits stated that the WPI does believe that the ‘hyper-active’ immune system often seen in CFS helps spread the virus throughout the body and she suspects that XMRV may have a ’tissue reservoir’ (ie be rapidly replicating) in the lymph nodes. Thus drugs that rebalance the immune system or just turn its activity levels down could be helpful.
(This is a tricky strategy; if a revved up immune system is indeed fighting off a pathogen, then turning its activity levels down could give the pathogen the break it needs to spread. If, on the other hand, the pathogen is using a hyper-active immune system to spread – then tamping down the immune system could be helpful).
About That PCR Test Again… – Nancy Klimas asked why VIP Dx was no longer using PCR? (PCR was, after all, the biggest finding in the Science paper). Dr. Mikovits reported that PCR was the least sensitive procedure for finding XMRV and that “the realization by the negative studies that only 1 in 1 million resting white blood cells harbors a copy of the XMRV provirus”. She also noted that it was more expensive. (Granted that XMRV is less easy to find by PCR than other tests….but its still hard to understand why the WPI didn’t realize XMRV was that hard to find until other groups start looking for it?)
The WPI’s Science article that reportedly answers many of these questions should be out within the week. If Nancy Klimas, a big early booster of XMRV, is still unclear about the PCR issue then you can be sure many other (less positively inclined) researchers are. It will be good to get that Science article out. (Dr. Klimas is waiting for more clarity on the testing front before she tests her patients)
XMRV – the Cause of ME/CFS? Does XMRV by itself cause CFS? Or is it one of several necessary factors needed for CFS to occur? Dr. Mikovits stated that XMRV is necessary for CFS but that the WPI’s current hypothesis is that it needs partners to cause it. She believes XMRV causes an immune deficiency which allows other pathogens to sweep in and cause the symptoms of the disease. She did leave the door open for XMRV by itself to cause CFS.
That Immune Deficiency – Do CFS patients infected with XMRV have any signs/symptoms that distinguish them from people who are not infected with XMRV? The ‘big’ questions just kept on coming. Were people with XMRV different from people who didn’t have the virus? This question is another big hurdle for XMRV. In order for it to be a major factor the patients with it will have to be different from those that don’t have it.
Not having the ability to track signs and symptoms in these two groups yet Dr. Mikovits didn’t know about those but she did note that of all the immune markers they tested (RNase L, other pathogens, cytokines and chemokines) that only one – Interferon alpha – correlated with XMRV. This, of course, is interesting given the WPI’s theory that XMRV causes immune hyperactivation leading to immune dysfunction – which opens the door to the other necessary co-factors such as pathogens, which take the patient down the same way HIV-associated co-pathogens take AIDS patients down.
Several immune abnormalities are associated with ME/CFS but XMRV, interestingly enough, does not appear to be causing them. It does, however, appear to be correlated with decreased levels of an important antiviral agent, IFN-a – which has not been typically associated with ME/CFS. It’s a strange situation, for sure but we are still in the early days of figuring XMRV out.
Dr. Mikovits said XMRV was not associated with the increased prevalence of any single pathogen but Annette Whittemore, if I understood her correctly, said XMRV was associated with the increased prevalence of pathogens in general. This suggests that XMRV could be acting in that same way HIV virus does; when it impacts the immune system different pathogens in different people tend to show up.
The Two Big Bugs in ME/CFS – another surprise came when Dr. Mikovits was asked how she felt HHV-6 and XMRV – the two big bugs in ME/CFS interacted. The fact that she has no reason, at this point, to believe that they (or any other bug) interact together at all, gives rise to some caution about XMRV’s role in CFS. She noted it is possible that XMRV infection could disturb the homeostatic equilibrium in the body that kept other viruses in check or that these viruses could send signals that up or down regulate XMRV activity.
A Big Question! – what percentage of CFS patients are infected? As the time goes on the WPI’s estimates of prevalence are rising. At the CFSAC meeting, Annette Whittemore said basically – if you have CFS then you’re infected and that seems to be being borne out by the WPI’s data. Dr. Mikovits said that 75% of the 400 people meeting the Canadian Consensus Criteria have tested positive for the virus and that there is antibody evidence of XMRV infection in another 10%.
Another Big Question! (And a bold answer) - Will treatment for XMRV eventually return CFS patients to health? Dr. Mikovits said she was “extremely optimistic that treatment of XMRV or its immune target(s) will restore CFS patients to at least 85% of the original health status even in the sickest of the sick.” Why such a bold prediction? Because the medical community has been able to do that with HIV – a virus that is far more virulent than XMRV is and which has more severe effects on the immune system. She noted, quite aptly, that some people are able to recover fully or nearly fully for years without ever having been treated for XMRV – something you could never say about HIV.
Co-occuring Illnesses – Dr. Garth Nicolson’s question about XMRV infection in family members surely revealed why Dr. Mikovits, so early on, got interested in co-occurring illnesses. She reported that two thirds of the XMRV positive patients in the Science study had a family member who also tested positive. She stated that most of them are ill with another disorder such as fibromyalgia or autism or cancer. She said the rates of cancer in some of these families is frightening.
(This in itself is a rather bold thing to say – cancer being such a frightening disorder. Just to be clear, although publications on this subject are pretty sparse – there’s little published evidence yet that cancer rates are increased in CFS and Dr. Mikovits findings findings – while certainly accurate -have yet to be validated statistically. Of course, it possible that XMRV could play a factor in several disorder; ie. that it may contribute to CFS in one person, FM in another, autism or cancer in another – that’s certainly the WPI’s thesis. We don’t know, though, that XMRV is a cancer-causing virus; in fact a recent study suggests that it may not be as effective at turning on ‘oncogenes’ as was once suspected. We’re still in the conjecture phase; surely, when/if XMRV is validated these types of studies will occur.)
Those XMRV Experts – in a more humorous vein Dr. Mikovits was asked about those 75 XMRV experts that were reported to meet at the Cleveland clinic in December. She noted she would be ‘surprised’ (make that very surprised) to learn there were 75 top XMRV researchers in existence at that time. It doesn’t take a genius to see how right she must be. XMRV was discovered (and then mostly ignored) by the scientific community in 2006. Until recently its been the focus of a couple of research groups in the US and Europe.
Was the Past Prologue? Are the percent positive rates remaining the same in people tested after the Science paper? Yes, as was indicated elsewhere – they appear to be; in fact the percent positive rates in co-occurring diseases (apparently FM and autism) appears to be higher than expected – about 35%.Add Your Comment