RESEARCH

The XMRV Buzz! - the Chronic Fatigue Syndrome / XMRV  News Page

• British Medical Journal Podcast on XMRV - It is XMRV month at the British medical Journal and they devoted their podcast to it. First they had on the controversial but always glib Dr. Wesseley.  He eschewed a psychological approach to the illness and instead focused on 'management' or 'rehabilitation'. Of course, we weren't going to get any plugs for antiviral treatments or anything like that but his management approach: getting away from the push/crash cycle of overdoing it and then crashing, focusing on sleep, etc.. at least as presented here, seemed  very mainstream if obviously limited. The one interesting moment to me came when he noted that while many pathogens can trigger CFS Epstein-Barr virus appears to be particularly apt at doing so and he stated they didn't really know why that was. He noted that in a 50 years or so our approach to this illness may seem very primitive indeed.
  
  Dutch Researcher: the highlight of the podcast was the appearance of the Dutch researcher leading the last XMRV study. He noted that because he was studying sporadic cases of ME/CFS that his results might not fit 'cluster' cases described in the original Science paper (see below). He stated that they used very high sensitivity PCR's - the same PCR's that the WPI researchers used - and that they looked again and again for the virus and really challenged themselves to find it. Because a fellow faculty member was actually studying XMRV in prostate cancer they had positive XMRV samples they could use to ensure that they could find the virus but, of course, as we know now they were unable to. The most striking thing about his talk was the fact that he'd heard that a good virologist in the US had been unable to find the virus as well. He believed that the original finding was probably either due to contamination  in the lab or to the fact that the original group was from a cluster. (WPI has said they were not from a cluster.) He believes that problems in chronic fatigue syndrome are rooted in the neurobiology in the brain, and that's where his research focus is.
  
  Epidemiology - Next up was an epidemiologist who noted the epidemiological deficiencies in the Science paper. These are pretty well known now and not really worth going over; few papers are perfect - if the epidemiological part of the Science paper had some flaws then sobeit. Her analysis indicated, however, closely these papers are looked at. The Science paper stated that the patients came from areas where there have been clusters or 'outbreaks'. It seems pretty clear now that while some of these patients may have come from areas where there have been outbreaks at one time, there is no indication that  these patients were the victim of 'outbreaks'. If they had been, however, that could have clearly made a difference because it's certainly possible that people who come down with ME/CFS as the result of an outbreak could have a different kind of CFS than people who didn't. (That does not seem to have been the case here; the patients came from several different physicians across US. Annette Whittemore noted that they were randomly picked out of the WPI biobank.)
• Phoenix Rising Forum Participants Report Low Positive XMRV Rates From their Physicians - these are all anecdotal, of course, and they don't really fit our polling numbers on the forums, but one forum participant stated that Dr. Levine told her that of 11 patients only one had come back positive for XMRV. None of Dr. Enlander's patients had apparently come back positive either but they were being tested by Dr. Kerr not by VIP Dx.  According to Dr. Enlander's website that paper is being submitted for publication; it appears we have another negative study result coming up. The polling numbers of the forums are about 50% for VIP Dx.

• XMRV Making Waves - XMRV may be temporarily be underperforming in chronic fatigue syndrome but it's doing quite well elsewhere in the research world. A report in MedPage Today indicates that the virus appears to be transmitted much the same way HIV is - through the blood and semen. At a Genitourinary Cancers Symposium ( once again in San Francisco) Dr. Klein (once again at the Cleveland clinic) reported that semen has factors in it that dramatically (unfortunately) enhance the ability of the virus to infect cells. He noted that HIV works the same way.
  
  Like other murine retroviruses XMRV also appears to integrate itself into genes that are related to tumor progression and metastasis. The work did suggest that anti-androgen (ie anti- steroid hormones like cortisol) substances do inhibit XMRV replication.

• BMJ on XMRV - citing the 'lively' response to their publication of a recent editorial on CFS, the British Medical Journal did what any media outlet would do when confronted with a hot story; they put XMRV on the front page of their journal and packed the Journal with XMRV articles; this was XMRV month at the BMJ. Lively was indeed the word for the 30 odd responses the Journal received, many of them lengthy and most of them taking the Journal to task for another behavioral, CBT promoting editorial on CFS. 
  
  The UK is as we know ground zero for the behavioral interpretation of ME/CFS The polite but condescending PR speak was, of course, present....the concern over the patients....blah, blah, blah. They noted, which we have heard, their concern over the patient cohort and the controls and the fact that their (and everyone else's) attempts at getting more information from the WPI failed. They went over the negative results and then admitted that they had rushed the last paper through to publication; a paper that in some respects, failed their standards. (An rather odd revelation from a paper called "Let's Proceed with Caution") They closed the piece in a rather snarky way appealing for research that this time, will be good enough. (No one beats the British at the velvet gloved knife in the back :)).
  

• Dr. Kerr Backs Out of XMRV Study - in surprise announcement Invest in ME announced that Dr. Kerr has backed out of study Invest in ME was planning to fund on natural killer cell functioning and XMRV. Dr. Kerr was a member of the second study not to find XMRV in ME/CFS.
  
  A person on the Phoenix Rising Forums reported  that Dr. Kerr was planning to use the positive samples from the first study for the NK study but didn't have positive samples  so the study was nixed. If that's true it puts an entirely different spin on a story that seemed, based on the  initial information from Invest in ME, that Dr. Kerr simply didn't believe XMRV was present in the UK. Hopefully Invest in ME will clear this situation up. Dr. Kerr is currently collaborating with the WPI on a multi-year study examining novel pathogens and immune functioning in ME/CFS. 
  
  Invest in ME, is still committed to exploring XMRV's role in CFS and will contribute the money gathered for the study to the Whittemore Peterson Institute.
• WPI to do UK XMRV Study - A participant in the WPI's Facebook site reported Dr. Mikovits sent her an email stating:

  "We are having an independent phlebotomy company draw samples in the UK in the next two weeks if you or others would like to participate send me your addresses and contact info ASAP. samples will be split and shipped half to an independent trustworthy lab and half to the WPI to determine XMRV status exactly as in the WPI Science study.
  
  Those who would wish to join this UK study please send your contact details to judym@wpinstitute.org. asap :-) 

• CFIDS Associations says Four XMRV Studies Not Enough - The CFIDS Association released a statement today stating that four studies aren't nearly enough to understand XMRV's connection to CFS. They acknowledged the frustration present after these studies but they also defended their critical analysis of XMRV and other studies stating that challenging study design, methods, etc. is is a vital part of the march of science which, of course, it is. At its best the scientific endeavor is like thrusting a piece of ore into the fire, chipping and burning away its impurities until it emerges, purified, with diamond-like hardness. The WPI has not yet commented on the latest study and the CAA also warned that they may not continue to comment on every negative study that comes out.
  
  After the abuse the organization got on their website and elsewhere for last analysis of the XMRV finding, this is hardly a surprise. A vocal minority of patients greets any negative assessment of XMRV as being something that borders on 'traitorous'. One blogger was so irked that somehow she managed to turn a critique of the XMRV study into a claim that the CAA was supportive of Dr. Wessely's efforts. Never mind the fact that the organization has never funded a CBT program and has easily funded more research on viral pathogenesis than any other support organization - in a heated environment like this the facts hardly count. It's difficult if not impossible for any support organization to comment critically and responsibly in an environment like this. Better to just bow out of the situation.
  
  Unfortunately doing that leaves the rest of us without one of the few informed voices we have. Few organizations, in fact, have dared to offer their analyses of the situation and the ME Association -which has its concerns about XMRV - has received similar (if less virulent) responses.  We've heard virtually nothing from the IACFS/ME or MERUK or other organizations probably because they know what to expect. For more on the CAA's statement click here.

• XMRV Under Fire - Check out this long take (beware!) from Phoenix Rising on XMRV to date including the disappointing studies, why they may be correct or not correct, how XMRV might be wreaking havoc, the testing situation and more.
• Mayo Clinic Researcher Talks on XMRV at the UC Davis Cancer Center in Sacramento, tomorrow.
• Prague Retrovirus Conference in April features researchers associated with XMRV (thanks to parvofighter for digging these up.

• Third Time Not the Charm - I recently posted a blog on the Dutch XMRV study results and a few other XMRV issues.



• Serology Test Results Starting To Come In - A participant in the Phoenix Rising Forums recently posted that she recieved her antibodies test result from Gordon Medical Associates (medical group working with the WPI). The test is not available to the public (she's part of a study) but this indicates it could be available fairly soon. My understanding that Dr. Mikovits believes this is, more or less, the definitive test for the virus.  She has reported on several patients who were negative for the virus using PCR who were positve using the antibody test. I believe she's been working with or is in collaboration with Dr. Singh in Utah on the test. Dr. Mikovits also said that the author of the big prostate cancer study that found no XMRV in Germany is rechecking his samples using this test. Below is the note this patient got from Gordon Medical Associates.
  
  I know you have been anxiously awaiting your XMRV results. We finally got a few initial WPI results, and your serology has come back positive. I think you know that serology does not necessarily indicate active infection. We don't yet have the other three test results for you, but they are being run.. . . We don't know yet what to do about it. Dr. Mikovits assures me that everyone who is positive will be given the opportunity to participate in further trials. We are taking this quite seriously, and we will be looking for what, beyond what we already do, would be most helpful.
  
  You are free to share your results, but people should know that we got very few results in so far. Some were control samples we sent in, so we don't have many patient results. They will continue to come in over time. Dr. Mikovits has been so busy speaking that it has been hard to do the testing. The speaking is good, because it brings awareness and money, so we need to be patient for the next step, but at least you have the beginnings of an answer for yourself. Check out the discussion here.
• Another Licensed Lab for XMRV Testing? - Forum participants also reported that RedLabs is working with the WPI to develop testing using their same procedures.
• National Cancer Institute News - Dr. Sandy Ruscetti was, if I remember correctly, a co-author (with her husband) of the Science paper.  (She is also the head of the Retrovirological Pathology Division (Cancer section). She's a key person in the field as she's been studying how mouse retroviruses (like XMRV) cause neurological disorders and cancer in mice for years before XMRV poppped on the scene. She's now applying that knowledge to XMRV. On her NCI website she reports that she is developing a rodent model for XMRV that will allow researchers to test the efficacy of drugs against the virus.
  
  Most interestingly she's examining how XMRV could cause its effects given it's lack of replication and low viral loads in the cells in the blood. She believes the proteins that virally infected cells put on their surface to indicate to the immune system that they're (in effect saying 'please kill me')are triggering an aberrant immune response that may be producing an neurotoxin.
  
  Dr. Mikovits connection with the Ruscetti's is so intriguing. What is the statistical chance that she would leave the employ of Dr. Ruscetti at the NCI and hook onto a mysterious virus in ME/CFS patients that would turn out to be Dr. Ruscetti's wifes speciality. It's unbelievable. If XMRV works out Dr. Mikovits was the perfect person to find it.
• WPI Opens Blood Transfusion Study - The WPI is interested in people who got ME/CFS sometime after receiving a blood transfusion. Simply fill out their research questionnaire and put blood transfusion in the applicable box.
• Cheney/Mikovits Q&A video Available - The video of the Q&A is now up.

• Third Time Is Not the Charm - Dutch XMRV Study Comes Up Negative - A small study found zero evidence of XMRV in chronic fatigue syndrome patients. This was undoubtedly the weakest study of the bunch; it used quite old samples and a watered down criteria and it involved a researcher reportedly committed to cognitive behavioral therapy. The furthest thing from a replication attempt an editorial accompanying paper nevertheless asserted that the methods should have been sufficient to detect the virus if it was there.
  
  All  of the early "quickie" studies appear to have their problems. Could those problems all amount to 'zero results'? We'll know when more comprehensive studies come out. We're still waiting for a study from the US. Dr. Mikovits stated that she expects some National Cancer Institute studies to be out shortly.
  
  Dr. Goff, someone associated with the process since the original paper, stated on Dr. Racanielo's blog that what's needed now is for different labs to test the same samples; that is, labs should find people who tested positive for XMRV via WPI or VIP Dx and test them. The CDC is reportedly doing this now.
  
  The WPI has not responded yet but it seems likely they'll simply state that unless someone follows their is procedures they are not going to find the virus. Dr. Mikovits reported that she's not worried about these validation attempts; as soon as someone uses the WPI's methods she expects they'll get the same results - time will tell. Check out a discussion here.

  The ME Association believes this third study considerably darkens XMRV's potential for being a major factor in chronic fatigue syndrome stating "these three negative studies now place a very serious question mark over the proposition that XMRV is present in a significant proportion of the ME/CFS population and that the infection plays a significant role in most cases of sporadic ME/CFS." With regards the different procedures used by the different studies they stated "the various laboratory investigations for finding XMRV have been carried out in very reputable microbiological research centres and involved retrovirologists of international repute."
  
  They believe the problem lies not in different cohorts or different geographical spread of the virus but in the laboratories doing the testing and urged that the same samples be sent to and tested by the variety of different lands. They also stated that "the MEA Ramsay Research Fund is very willing to consider funding high quality research proposals".
  
  Whereas they may at times take some flak for doing so both the ME Association and the CFIDS Association of America should be acknowledged for their willingness provide their analysis of what's going on to the patient population while other groups (MERUK?, IACFS/ME) have hung back. Remarkably, the our professional research organization (IACFS/ME) has contributed little or nothing to the discussion on XMRV.

  Ongoing 'Study' Continues to Find XMRV - one fact that is not being mentioned is that one group has been and continues to find XMRV - daily - that's the VIP Dx labs.

  I had heard that VIP Dx shut down because they couldn't find the virus anymore -which suggested that it was a contaminant and that the contamination had been cleared up; ie no more XMRV. So I asked them about that and this is what they said. 
  
  Of course we have to bear in mind that one laboratory - VIP Dx - is finding XMRV all the time. I had heard that they were no longer able to find XMRV using PCR so I asked them. This is their answer.
  
  
  There is so much MIS INFORMATION. In no way did VIP Dx stop testing for XMRV using PCR. The culture is done by a PCR method. We streamlined the testing to avoid the high costs that doing both the first run PCR and then the extraction and culture had. We still extract and then grow cells for culture and run the culture test. By streamlining our processes, we have developed a test method that gives higher sensitivity at a cost savings that has been passed on to our patients. Our license agreement with WPI includes consultations and quality assurance by their researchers that we are running the best and most sensitive test available at this time. This high sensitivity method is producing good results in detecting the virus.
  Feb 24th
  
  • The CFIDS Association webinar on its research program is up on YouTube. There wasn't much on XMRV, of course, but it was fascinating look at what is turning out to be a very innovative research program. It was a nice break from all the turmoil surrounding XMRV. You can find it here.
  • Dr. Mikovits has been answering emails and she answered one of mine. We heard rumors that the CDC was up at the WPI- that was untrue but the WPI has shared it's reagants and antibodies, etc. with them. The CDC is apparently contacting other labs as well for their specimens and doing extensive testing.
    
    Dr. Mikovits reported that the vaunted DHHS study is still, 3 months later, in the 'design phase', which hardly suggests the government feels any urgency about it. Other agencies within the govt. are moving quickly. The CDC is acting on its own and Dr. Mikovits reported that she expects the NCI (National Cancer Institute) to PUBLISH SEVERAL PAPERS SOON both on XMRV in CFS and prostate cancer. Dr. Mikovits, of course, hails from the NCI.
    
    In her email she seemed both a bit exasperated and confident stating "we don't lose much sleep worrying about replication, we are certain that once someone tries to do it as in Science paper (they) will find it". The UK researchers didn't communicate with Dr. Mikovits or the WPI but its hard to imagine that she's not in touch with her former colleagues at the NCI researchers - given that her confidence is a good sign perhaps some positive papers are on the horizon. She also said that the "HIV docs get it 100%"
    
    The WPI has been questioned a bit for putting a test out so early. Dr. Mikovits clearly stated that the appearance of the Cooperative Diagnostics test, just a week after the paper came osiut, pushed them to bring out a test earlier than they had planned. She said they asked them to cease and desist and they refused. CD has its proponents; a member of the Forums has been in touch with them extensively -and is impressed with their work; only time will tell how the CD situation shakes out.
    
    She also stated that based on their facts so far it seems that XMRV is more prevalent in the western US than the eastern US. The fact the XMRV samples were so genetically was suspicious as that can imply they originated from one source (a contaminant) at the WPI or the Cleveland Clinic's One theory posits that a particularly powerful sample of XMRV could have escaped contaminating the lab and the CFS samples (but somehow not the healthy controls?) or that the problem originated at the Cleveland Clinic. Dr. Mikovits said, however, they now had 200 strains isolated and they're sequencing them and finding more variation than in the first six.
  Feb 22nd
  
  
  • More From the San Francisco Retroviral Conference - The Forum participants are continuing to dig up more info on how XMRV fared at the big (apparently one of the biggest) retroviral conference in San Francisco.
    
    Emory University is apparently big in hunt for XMRV. We know that XMRV is able to infect cells called fibroblasts in the prostate but that epithelial cells express a lot of antigens (markers on their surface suggesting that they are infected) as well. Dr. Mikovits talked about an amino acid 'loop' that XRMV used to gain entry into cells. This team showed that fibroblasts had this loop but the other cells - which appeared to be infected - didn't, which suggested to them that XMRV has more than one way to get into a cell. What's so interesting about these other cells? They happen to be smooth muscle cells; these are cells  that dot the linings of our blood vessels and tell them to open up or constrict. Researchers have conjectured the blood vessel problems could cause many of the abnormalities in the brain and elsewhere in CFS - an intriguing idea given that XMRV can apparently infect them.
    
    This group is also looking at RNase L. RNase L has not appeared at these early stages to determine IF one is infected but thiese researchers believe it could determine which cells are infected.
    
    There's much more coming from the conference. This conference and the months ahead are clearly going to be head turners for all of us - not just in the things that are learned - but in how quickly they are learned. It looks like we're going to see what scientific community can do about an issue it wants to study. It may be that we'll know more about XMRV over the next year or two that we know about chronic fatigue syndrome - a sad even tragic statement in one way but a promising one in another. Stay tuned.
  
  
  Feb 21st
  
  
  • Complete Mikovits-Cheney Transcripts Available - it was an interesting if partly inaudible talk but the transcribers on the Phoenix Rising Forums somehow cut through the interference to produce a clean copy. You can find the first half here and the second half here.
  • San Francisco Retrovirus Conference XMRV Updates - XMRV infection in primates has thus far not produced any visible symptoms - no fevers - no real suggestion of an infection. Abbott Diagnostic researchers (not the Abt association with the CDC) have developed antibodies to various proteins on XMRV and have been able to detect them in humans but in only a very few of them (3/2851 blood samples) - which doesn't nearly, of course, reflect the 4% prevalence in healthy controls in the WPI study or the 1.5% prevalence in the Japanese study. Dr. Hackett noted that could reflect the virus's life cycle (was is hidden?) or the time between infection and disease or other factors. (These may be the viral reservoirs Dr. Mikovits was talking about.) ifAbbott Diagnostics has been interested in developing a diagnostic test for XMRV for about three years.
    
    Neither Dr. Coffin and Dr. Goff are jumping ship after the two negative studies; they've seen the ups and downs of retroviral research before. Dr. Coffin, in fact, appears to be an enthusiastic about XMRV as ever stating "There is no question I think that the virus is real and that the virus is infecting some numbers of people. And it’s VERY (Coffin's emphasis) important to figure out where it is going as far as all of its disease associations are concerned… it’s very early days… if you think back to 1983 and what it was like with HIV, how uncertain things are, how long it really takes to grind the sausage (!) and come to a consensus to understand what’s really going on…We’re still in a pre-consensus stage with this virus, and although it’s annoying and confusing, it’s really exciting."
    
    From Dr Goff: “We know very little about its mode of transmission. We don’t have any reason yet to be excited about any pathology but it’s certainly something we want to pay attention to and make sure we’re not missing anything.
    
    ... And so we live as humans with a lot of viruses that are non-pathogenic or that are not detrimental to the population… ( think people want to know a lot of simple things. It would be great to know the origin – if it was a mouse…We’d love to know the tissues in which it replicates, and we know a little about that now because we’ve studied the virus in culture....the most important maybe is the prevalence in the human population, which we don’t know….
    
    Interviewer: Are there any other colleagues working on this, or is there some sense of urgency, or just casually looking at it…
    
    Goff: The NCI is pretty serious about it, they don’t want to miss anything. And they want to play a role in identifying the properties of this virus and its potential risks. So they’re pretty serious about it. The range of anxiety is from very mild to the worst scenarios: “Gosh, do we need to be worried about it getting into the blood bank. Do we need to be concerned if it’s really causing a certain subset of prostate ca. And the latest is the potential link reported last year of an association with CFS which would be very exciting because that’s a disease that has struggled to find a viral cause.
    
    Interviewer: So that might be the cause?
    
    Goff: Could be…I talked about the behavior of the virus in culture which in our hands is quite vigorous. It’s a very easy to grow virus in the right cell types. Several of the talks today talked about some of the behavior of the virus, for example it’s androgen responsive, or GRE responsive. Hormone responsive – the receptor that it uses. Both of which bear on cell types in which it can be found. The most recent exciting work of course is the discovery in Chronic Fatigue Syndrome and that too is very controversial. Some people are finding it, some not. I think that will have to be worked out in the coming months and years. " (thanks to Parvofighter for the transcriptions).
    
    The first media report on XMRV from the conference appeared on MEDPage Today
  
  
  Feb 20th
  
  
  • The Mikovits Cheney talk had good visuals but problematic audio with Dr. Mikovits sounding at times like she was talking through a metal funnel but clean transcriptions of the talk by the erstwhile Phoenix Rising Forum participants are already going up. Check the first out here.
  • Retrovirologists Speak - We have video from retrovirologists at the 17th Retroviruses and Opportunistics Infections in San Francisco talking about XMRV. Dr. Goff reflected on how easy it is to grow XMRV in the right cell types - an important finding because that allows researchers to intimately study the virus. The fact that the virus is easy to grow in hormone sensitive cells is important because those are the types of cells that the virus will probably be found most readily in the body. (This apparently suggests that immune cells will not be the main reservoir; ie the main locus replication in the body, and it, of course, fits with the finding of the virus in prostate tissues).
    
    The next speaker's short presentation suggested that the research community is vigorously going after this virus. Her work involved Emory University in Cleveland Clinic (CC collaborated with WPI on the Science paper). It's very exciting work. The NIH has talked about the need for an animal model of CFS for many years; this is essentially an animal they can give CFS to and then study it in detail to try unravel what's going. They've ever done a darn thing about it - no surprise there - but the Japanese are using a rodent model to study this disease. Rodents are cheap and easy to work with but this group is already using a primate (rhesus monkeys). Primates, of course, share many more characteristics with humans than monkeys do and they're also much, much more expensive. The fact that this Emory University researcher is already using primates suggests they're quite serious about XMRV.
    
    They're looking at these monkeys very carefully - she just gave us a little glimpse of what they've found - but thus far XMRV is setting up camp in the lymphoid organs and the reproductive organs (prostate, testes, cervix, vagina)with of these animals. The lymphoid organs (spleen, thymus, bone marrow, etc.) create lymphocytes (among other things) - the white blood cells the WPI was studying.
  • Groom Study Issues - We've been digging deeper into the Groom UK XMRV study on the Phoenix Rising forums with the assistance of members with technical expertise in this area. Questions regarding the necessity of culturing the cells start to increase viral expression - before the PCR is done - have come to the fore. My understanding is that there’s only one reason to culture cells and that’s to up the levels of a low level virus. The Science paper has three sections where they culture the cells; they obviously did that for a reason – yet the Groom group ignored it and simply used unstimulated cells.
    
    After the fact it seems inexplicable - at least to a layman - that they could have ignored such a fundamental aspect of also wonders why after their hundreds of samples started to come up negative why they wouldn't start culturing cells to see if that made a difference? Perhaps they thought their increased sensitivity would enable them to find the virus regardless of whether the cells are cultured or not. Hopefully we'll get answers to these questions at some point.
    
    Someone on the Phoenix Rising Forums just posted a list of standard blood isolation and amplification procedures for HIV http://forums.aboutmecfs.org/showthread.php?3133-XMRV-CFS-UK-study-II/page52 and stated that the WPI followed most of them and the UK groups followed few of them. If you look at the methods sections of both papers you’ll see that the methods section for the relevant procedures are longer in the WPI paper than in the UK papers.
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  Feb 19th
  
  • Cheney Clinic - the latest XMRV finding has deterred the WPI not at all; they appear confident in the strength of their findings and Dr. Mikovits will take all comers via speakerphone with Dr. Cheney. Dr. Cheney has limited questions to Cheney Clinic subscribers but Andrea Whittemore will take yours and pass them on at andrea.whittemore@wpinstitute.org.
  • The video from Dr. Mikovits talk at the Cheney Clinic is still not up. It should appear here at some point.
  • A Guide to XMRV Research: the WPI Answers Back - the inability of the second UK XMRV study – this time from a ‘friendly’ research group headed by Dr. Groom – to find any XMRV in a very large sample of patients was rough news for sure. The ME Action Group in the UK took a rather resigned tone in their response while Dr. Vernon highlighted a few methodological issues but mainly concentrated on questions about that original cohort. Neither presented much good news for CFS patients as a cohort answer to the current problems would mean the virus is only present in a very select subset of patients.
    
    In their response to the latest paper the WPI defined the pitfalls they believe researchers face in validating their work – thus basically giving them a guide on how to find XMRV – and doing everybody a big favor.
    
    No Replications Studies Yet Done: They noted that no one has yet attempted to replicate, i.e. exactly duplicate, their original study. In the best of worlds, of course, a true replication study isn’t necessary and is, in fact, irrelevant. How one found the virus, after all, is not particularly important; pathogens can be uncovered by several techniques and researchers typically use different techniques to validate the presence of a pathogen. In fact, a positive validation study using a different technique is considerably more valuable than a replication study because it definitively demonstrates the pathogen is there. It’s only when the validation studies are unable to validate a finding that the issue of a true replication study becomes important – as it now has.
    
    Looking Back – This replication/validation issue was prominent in Dr. DeFreitas retrovirus of almost 20 years ago. The CDC and Gow teams were well versed in retrovirology and had used standard procedures again and again to find viruses. Given their track record they felt little need to change their procedures. (Ultimately the CDC did at least to some degree). But Dr. DeFreitas felt her bug was different. Given her inability to replicate her results she may have been wrong; the question now is whether XMRV is different as well.
    
    Both UK studies used standard XMRV samples to ensure they could find the virus – and their results indicated that they could – but they couldn’t find it in the CFS patients. It may be important, though, that outside of one Japanese study these are the first attempts to find XMRV in the blood and researchers are treading new ground here.
    
    We know that two US prostate cancer studies found XMRV but two German ones did not. We know the German prostate cancer researcher is redoing his study using a different technique. It’s clear that, irrespective of CFS, the field of XMRV research (as small as it is), is quite muddled at this point – perhaps we shouldn’t be so surprised about the bumps in the road encountered thus far.
    
    The WPI took the UK study to task somewhat for not using their reagents, blood, etc. stating that there is only one way to look for XMRV in the blood that’s been validated and that’s their approach and they have a point. The WPI was the first group to ever look for XMRV in the blood and they validated their results as best they could using the Cleveland Clinic and NCI labs. To be fair the Groom study researchers, some of whom have long track records in CFS research, didn’t have any reason to think their procedures wouldn’t work since apparently they do work for most viruses. It’s possible that both they and the Imperial College researchers underestimated the difficulty of finding this virus in the blood.
    
    To their credit they were careful not to overstate their case simply stating in the paper they were unable to find XMRV DNA in their samples and not making broad conclusions about XMRV and CFS. Once the paper came out they’ve stayed out of the spotlight – - they appear to be waiting to see what other studies turn up.
    
    The WPI’s Issues
    
    Most of the issues pointed out by the WPI don’t appear by themselves to be able to account for the differing results in the UK. String them together, though, and you get an interesting scenario.
    
    
    • Blood Harvesting and Storage – The idea that different blood storage and harvesting procedures could’ve altered the results seems possible but seems unlikely (to this laymen) given that the Groom study used three cohorts from three locations -each of which could have used different storage techniques. We know that XMRV is robust enough for Dr. Peterson to be able to pull XMRV out of a 20 year frozen sample but the possibility does remain that the Groom study inadvertently used blood storage techniques suitable for other viruses but not for XMRV. Laymen’s Conclusion – possibly a significant factor but not likely.
    • Different Patients - The idea that the WPI had one set of patients and everyone else had a very different group has come up again and again. The very large size of the British study with patients from several different groups appears to make this scenario an unlikely one (and a decidedly unattractive one since then XMRV would apply only to very special patient groups.) On the other hand some differences in patient selection could start to lower the prevalence rate.Laymen’s conclusion – not ‘It’- but a possibly a contributing factor.
    • Different Geographical Prevalence - that XMRV is simply not found in the UK (but is found in the US and Japan) seems have little plausibility given the fact both Dr. Mikovits and VIP Dx labs have stated they’ve found XMRV in samples from UK patients but it’s certainly possible that XMRV could be less prevalent there thus driving down the prevalence a bit (more?).Laymen’s conclusion – not It either but prevalence rates could be lower – we just don’t know.
    • Very , Very Low Levels of a Very Difficult to Detect Virus – While the other issues could reduce an investigators ability to find the virus with the exception of the blood storage issue it’s hard to believe they could result in being unable to find any XMRV in a large group of patients. This low viral level issue seems to be more significant, however.
    
    
    The WPI did two things the other groups didn’t do to find the virus.
    
    • They Usually Grew the Virus in White Blood Cells First in Order to Increase its Numbers. (This presumably involves hitting the white blood cells with a substance designed to enhance viral replication). Dr. Mikovits reported earlier that while XMRV appears to be able to readily infect immune cells it simply doesn’t have the tools to replicate readily in them – hence its viral loads are expected to be low. Not culturing white blood cells first could, then, reduce prevalence rates markedly – but note not completely – as the WPI said they usually, but not always, had to use this technique. Still the fact that the WPI researchers cultured their cells in the Science paper was a clear sign - a red flag one think - that viral loads were pretty low.
    • WPI researchers Had to Search Multiple Times Both in Time and Space to Find the Virus - Not only did they look at a sample multiple times sometimes they had to look at samples taken at different times from the same patient in order to find the virus. The UK studies, on the other hand, presumably looked at the same samples once or twice. (The Retrovirology study looked at their samples twice, once using a more sensitive technique).
    • Does perhaps a bit different cohort, perhaps reduced rates of XMRV infection in the UK, maybe some blood storage issues and a much more difficult to find than expected virus equal zero findings in two UK studies? With true replication studies purportedly on the horizon we’ll know in the not too distant future.
    
    A Confident Group – The WPI asserted, as well, that the best test of XMRV infection, given the difficulty finding it using PCR, is an antibodies test. The Retrovirology group did use an antibodies test but the WPI asserted that it was flawed and theirs is superior.
    
    At the end they stated the only reliable to find XMRV in CFS is to use their approach and basically that no-one’s going to find it until they start using their techniques.
  
  
  Feb 16th
  
  
  
  • Dr. Vernon on the UK XRMV Study - as expected Dr. Vernon delivered a comprehensive overview of the latest XMRV study in the Retrovirology journal. Dr. Vernon spent some time making clear who just who did this study; it was basically the best of UK retroviral researchers (one 'world-renowned') plus top ME/CFS UK researchers with long histories of CFS research. 
    
    Like Dr. Shephard she clearly felt this paper presented a significant hurdle for XMRV. She reported that the PCR methods were identical to those used in the original paper.  When those techniques didn't find any virus they looked harder using a different, much more sensitive PCR technique. Dr. Vernon stated it could be 'considered better and more sensitive' than used in the original Science paper and they stil came up nothing.
    
    If I understood it right, Dr. Vernon also put one limb of the Science paper's argument in doubt by noting that the cross-reactivity in the antibody tests in this study suggested that the antibody tests in the Science paper could have been due to exposure to a different virus.
    
    Again: the Wrong Patients? - The sample came from three cohorts. Dr. Vernon noted that because the blood from the biggest cohort came from relatively 'new patients'  (1-4 years) it's possible that XMRV doesn't show up until later in the illness. This is not unheard of. My understanding is that HIV often hangs out in the spleen and other immune organs for several years before it wallops the blood cells and the low copy level of XMRV suggests that it could have another locus in the body. Dr. Vernon discounted this idea to some extent by noting that Dr. Kerr, a prominent ME/CFS researcher (who derives his funding from several ME/CFS support groups), helped conceive the study and presumably would have taken care to include more 'WPI-like' patients in the other cohorts. Still it's a possibility.
    
    Did a longer duration, sicker, perhaps more immune suppressed group have a more detectable infection? Not according to Dr. Mikovits; she recently reported that patients in the study simply needed to meet the Fukuda or Canadian Criteria for inclusion; they were not particularly ill or disabled.
    
    Still, Dr. Vernon took the WPI researchers to task for not releasing information regarding the illness duration, illness severity and treatment history of that original cohort, going so far as to suggest that their inability or unwillingness to do so could imperil the further research into the XMRV/CFS connection. She is clearly worried that more results like this one - which she warned will be forthcoming unless researchers know which patients to study - will dampen scientific interest in XMRV and CFS.
    
    Hiding out in the UK but not the US? - She also noted that the virus could be present in such low levels that even with their more sensitive techniques the Retrovirology researchers couldn't find it. That begs the question, though, why the WPI with their less sensitive methods was able to find it both before and after the Science paper in both US and UK patients.  (Dr. Mikovits noted that VIP Dx labs sometimes searched 3 or 4 times before they found the virus - did the WPI researchers do the same with their Science samples?)
    
    The virus is clearly hard to find, that's for sure; of the 27 people on the Phoenix Rising Forums VIPDx Poll only about 20% tested positive to the PCR test but 20% is still light years different from the zero percent the Retrovirology researchers reported; given their background they clearly would have loved to find 20% positive rates.
    
    Yes, perhaps there weren't enough long duration and severely ill patients in the Retrovirology study and the Imperial College study but it still seems hard to believe that the wrong patient cohort is the cause of "zero percent" positive rates. The cause of the conflicting study results is still very unclear.
    
    Dr. Vernon made it clear that the DHHS studies will use different techniques, including the WPI's original techniques, to examine people who tested positive for XMRV via the VIP Dx lab test. This will help determine why the discrepancies are showing up.
    
    Everyone's Doing Everything Right! - This has been a tough couple of days for XMRV but check out this take from a researcher in ScienceNow. It suggests that disparate results happen even in the best labs. 
    
    "discrepancies between labs are common, says David Griffiths, a virologist at Moredun Research Institute in Midlothian, United Kingdom, who has studied previous claims for retroviruses as the cause of chronic diseases. He also notes that he cannot find serious flaws with any of the published studies: "All the people involved are doing things exactly as they should be." For the time being, then, the XMRV results will remain frustratingly ambiguous. As Griffiths says, "There must be an explanation for why disparate results are showing up, but it may not be an easy thing to turn up."
  • For the Full Text of Dr Vernon's Analysis
  • The ME Association is one of three ME/CFS groups that has (CFIDS Association, MERUK) provided technical analyses of the XMRV studies. Their conclusions, written by Dr. Charles Shepard, indicate they now believe that with this new finding that the XMRV finding has a big hurdle to overcome. Specifically, they point out their inability to find 'any significant fault with the very thorough laboratory methods' in the study.
    
    They noted that there is still no international agreement regarding how to search for this virus and they appear to be as puzzled as the rest of us regarding the 'starkly' conflicting results. They state the need to find the 'exact reason why there is such a stark difference between the negative UK and the positive U.S. results.' They are also trying to test UK patients with XMRV positive results for the VIP Dx Labs to see how they fare using these different techniques.
    
    We have yet to see a US replication or validation study; it's unclear why a US study would have different results but thus far that strange pattern persists; every study that has looked for XMRV in the US has found it while every study that has looked for XRMV, whether in CFS patients or prostate cancer patients, has not. The ME Association's statement is below:
    
    ME Association's Statement on the Second UK XMRV Study - "These new negative results, along with the negative results from Imperial College, are in stark contrast to the very positive US results reported in Science and they clearly place a large question mark over a possible link between XMRV infection and ME/CFS. And while the two UK studies have been criticised for not being pure replication studies, because they are not using exactly the same criteria for patient selection, a significant proportion of these UK patients in both studies must have also met the Canadian clinical criteria. And while differing laboratory protocols were used to test for XMRV, it is very difficult to find any significant fault with the very thorough laboratory methods used in the new UK study. 
    
    
    Although some scientists will now conclude that the XMRV and ME/CFS debate is over, no firm conclusions can be drawn until we have the results from other studies that are being carried out, or have been completed, that are designed to try and find evidence of XMRV in people with ME/CFS. Further results from outside the UK should be appearing in the scientific journals in the coming weeks and months. Whilst the two UK studies do not provide any evidence for XMRV infection, they do not completely eliminate a role.span class="Apple-converted-space"> 
    
    One small but important add on piece of research that The MEA is continuing to pursue is to see if some of those people in the UK who have tested positive for XMRV using the US test can now be retested by one of the UK groups. It would also be very interesting to see if a mutually agreed cohort of CFS blood samples and control samples can be tested by all three UK and US research groups to see if they produce the same XMRV results.
    
    In the meantime, as the UK researchers point out, it is important to compare samples and protocols between different laboratories in different parts of the world because we do not currently have international agreement on which is the most effective way of testing for evidence of past and present XMRV infection. We also need to find out the exact reason/s why there is such a stark difference between the negative UK results and the positive US results
    
    The ME Association will continue to take a cautious, open-minded and questioning approach to XMRV. Our advice on XMRV testing remains the same. We do not believe there is any point, at present, in spending a large sum of money on commercial blood testing for XMRV because the presence of this infection has not yet been shown to be a diagnostic marker for ME/CFS or an aid to management. The accuracy of some of commercial testing also remains uncertain.
    
    The MEA Ramsay Research Fund - http://www.meassociation.org.uk/inde...=30&Itemid=205 - will continue to consider applications for research funding for any aspect of XMRV research."
    
    Dr. Vernon from the CFIDS Association is up next. She tends to give a much more technical analysis of the studies.
  • Speculation on the UK XMRV Study From a Layman  - This really is a conundrum. My understanding is that the WPI is now using Dr. Singh's XMRV specific antibody test which is showing  INCREASED not decreased rates of positivity. It appears that just as the WPI is getting more and more internal evidence that they're right these papers are coming out suggesting that something went wrong. The first question always appears to be whether what the WPI found is an endogenous retrovirus - a piece of junk DNA from an old mouse retrovirus in our genome. They sequenced 2 and a half strains of the virus and compared what they found against our entire genome against our entire genome and found nothing. That's one of the reasons Science took the paper - they convinced them it was not an endogenous retrovirus. 
    
    If it isn't an endogenous retrovirus then what is it? Bear in mind that we have yet to see a 'replication study'; no one has yet followed the WPI's study to the letter. Different groups are doing different kinds of PCR and different kinds of antibody tests. Theoretically they all should match up but they're not; the twists to this story are amazing and unsettling but the WPI has the National Cancer Institute and the Cleveland Clinic behind them; they produced 'the best' first paper possible and it landed in the most prestigous journal in the world. Other groups are doing more comprehensive analyses of the WPI results; Dr. Klimas said this was going to be an up and down process - she was clearly right!
  
  
  Feb 15th
  
  
  • Deja Vu in the UK - XMRV CFS Study Comes Up Negative Again! UK researchers are not winning the hearts and minds of CFS patients - that's for sure. Just a couple of uplifting weeks after Dr. Mikovits displayed so much enthusiasm and confidence in XMRV the other shoe has dropped. An Imperial College researcher said another negative study was coming and here it is; this UK study also failed to find virtually ANY evidence of XMRV in a large number of CFS patients. This study was similar and different from the Imperial College study.
    
    Annette Whittemore said to be cognizant of who's doing the studies - in this case, though, there doesn't appear to be any bias to question, no damning history of behavioral emphasis to reflect upon; two members of the study, Dr. Kerr and Dr. Gow, are long term ME/CFS researchers committed to a pathophysiological interpretation of this illness. (Ironically it was Dr. Gow that refuted Dr. DeFreitas finding 25 years ago).
    
    Indeed, the paper went to some lengths to praise the Lombardi Science paper stating the "apparently compelling evidence against the possibility of laboratory contamination" and the immune response against XMRV the researchers demonstrated was present. They stated that they set out with 'the intention of confirming the Lombardi' study.
    
    PCR Tests - This was a large study that looked at well over 500 CFS patients and controls from two cohorts in the UK and Scotland. They first looked for sequences on two the three genes XMRV possesses. When they didn't find anything the first time they looked again using a more sensitive assay.
    
    Immune Teststs - Unable to find evidence of XMRV by PCR they looked for signs that the patients immune systems were reacting to it. To do this they obtained some 'neutralizing antibodies' against the 'env' protein found in the family of mouse retroviruses. Antibodies neutralize retroviruses by attaching to them and preventing them from getting their hooks into cells. They also raise a red flag to the immune system to come and attack. As they examined this set of antibodies they were able to identify one that was specific for XMRV and they used it to search for the virus.
    
    The neutralization test is a rather indirect one; they apparently add the antibodies to the sample and then (somehow) test the sample for 'infectivity'. Since the antibodies attach themselves to the retroviruses the degree of infectivity should go down a certain amount and in a couple to test cases they confirmed this. When they ran the neutralizing antibody test on the 142 ME/CFS patients none of them met the criteria for infection. Ironically, 14% of the healthy controls from one of the healthy cohorts tested positive for infection, altho later testing suggested it was do to a different mouse virus.
    
    They stated that they were 'confident' that their 'PCR assay is more sensitive than the published single round PCR method and should have possessed the necessary sensitivity to find XMRV'.
    
    Two Different Tests : Two Different Results - The WPI has backed away from the PCR test because of its inability to detect XMRV at very low levels and their associated lab VIP Dx is not longer offering it. This could not be a reason, of course, for the zero results seen in this test - the WPI's PCR test may not be perfect but it appears to be able to find most instances of infection. We also know from Dr. Lombardi and from patient reports that the WPI's test IS finding XMRV infection in UK patients. Why they are finding it and two UK groups have not, is, of course, the big question. Either the patients are very different or the tests are. Since it seems unlikely that that the patients are THAT different its pretty clear that the WPI's test is quite different from these other groups.
    
    Validation Not a Replication Study y - It's interesting, by the way, that this UK group - with its ties to the WPI via Dr. Kerr - did not appear to avail itself of the WPI's assays or or Dr. Singh's antibody tests. Since the group didn't appear to use the WPI's methods this is a validation study not a replication study; its was an attempt to validate the WPI's claim that they'd found XMRV not an attempt to determine if the the WPI's methods worked.
    
    These are still just the first few of the XMRV studies we expect to come out but its remarkable turnaround given the lengths the WPI, researchers from the NCI, and the Cleveland Clinic went to in that compelling Science paper (Dr. Coffin called it as good a first paper as they get) to demonstrate the presence of XMRV. The fact they were able to show that this virus was able to infect previously uninfected cells and show a virus budding out of them still seems - at least to this layman - to be the most singular and important finding to date.
    
    The Scientific Director of the CFIDS Association, Dr. Vernon, will reportedly release an analysis of the study tomorrow, giving us a much needed expert overview of the situation.
  • The complete paper
  • ME Association's brief response
  • Professor Racaniello's Virology blog on the study
  • Discuss the results
  
  
  Feb 13th
  
  
  • Dr. Bell on the Move - Our most prolific XMRV lecturer is crossing the border to give a lecture in Toronta, Canada on March 6th. The talk is called “Current Findings and Research into ME/CFS: XMRV Virus and What It Means” The talk is courtesy of the Myalgic Encephalomyelitis Association of Ontario and the Environmental Health Clinic, Women's College Hospital: Saturday, March 6, 2010, 1-4 p.m. Women’s College Hospital Auditorium, 76 Grenville Street, Toronto Suggested Donation at the Door: $10
  • YouTube Video of DeMeirleir talking on ME/CFS, H2S, XMRV and more in Sweden (Nov. 2009) on YouTube. Part I / Part II (XMRV is in Part II.) Dr. De Meirleir was the main driver behind the work on the immune defect (RNase L) that lead Dr. Mikovits to search for XMRV in chronic fatigue syndrome patients. Dr. De Meirlier, however, switched his research interest to hydrogen sulfide about the time XMRV was found in RNase L deficient prostate cancer patients - just missing the boat on what may be the greatest find in ME/CFS history. It's very possible that without Dr. De Meirleir's work the XMRV/CFS connection might never been made.
    
    Dr. De Meirleir said he'd known of a retrovirus in chronic fatigue syndrome for several years and referred to Dr. DeFreitas work in the early 1990's (apparently with regard to another retrovirus). He believes that some virus mildly depresses the immune system but there are other factors. He believes its part of the puzzle but not the complete picture. He noted that it 'seems' to be a new virus (we don't know for sure) and referred to earlier epidemic occurrences of the disease that were caused by other pathogens.
    
    He was grateful for the increased rate of basic research XMRV will inspire but stated the patients will have to continue to be patient as it will take some time after that for the clinical ramifications (ie possible treatments) of XMRV to become clear. Dr. DeMeirleir made the point that he's getting good results with his immunomodulatory and other treatments - stating that for patients under 30 he is disappointed if he doesn't get 90% improvement (?!).
    
    (Dr. Mikovits is much more enthusiastic about quicker treatment possibilities for patients, stating in an e-mail that she envisioned many patients being in clinical trials just six months from now. She said she began getting calls from pharmaceutical companies the day after the Science article hit. These companies have many retroviral products sitting on their shelves that never made it to market with HIV. Some have gone through the steps needed to prove they're not dangerous; all is needed are trials demonstrating effectiveness. Dr. Mikovits has been shipping them cultures and special cell lines they can use to test their drugs against XMRV. Sign up on the WPI's webpage to participate in upcoming clinical trials.
  • The BEST Studies - After Dr. Mikovits talk we were able to add a couple more studies to the XMRV Study page and we've now got about 20 or so groups we think are trying to determine the incidence of XMRV in ME/CFS. But which ones are the best? Which will we learn the most from. My guess is that two sets of studies will make the most difference for us.
    
    The Big Cahounga's - First and foremost are the big studies from major labs that have alot of standing in the scientific world. These would be the DHHS studies involving the NHLBI (National Heart Lung and Blood Institute), the NCI ( National Cancer Institute) and the CDC. These studies will do more to convince or not convince the scientific community of the importance of studying XMRV. Given the excitement generated by XMRV its possible that interest in the pathogen could survive some negative studies by these groups but for the big federal money to show up one would think these studies need to work out.
    
    The ME/CFS Professionals - Let's jump ahead and say those studies all work out - what then? The big winners for us will be studies done by researchers such as Dr. Montoya, Dr. Kerr, Dr. Klimas, of course, Dr. Mikovits and Dr. Peterson and researchers of their ilk. Since these researchers already have so much information on chronic fatigue syndrome and to appear to have banked their samples all they need to is retest them and then add that data to the mix. Dr. Montoya should be able to quickly determine EBV positive patients are at increased risk for XMRV infection or if patients 'failing' repeat exercise tests are. Dr. Klimas will be able to zero on the role natural killer cell functioning plays in XMRV infection. With his now huge database of gene expression results, Dr. Kerr will be able to see if overactive or underactive genes are associated with XMRV.
    
    The BioBank Win - You can quickly see just how advantageous sample repository's such as the WPI repository or the patient BioBank the CFIDS Association of America is building as a part of its international research network. Once a new finding is found a BioBank can literally cut years off a research project.
  • MISSING IN ACTION - The NHLBI is working away on the blood, the National Cancer Institute has been all over XMRV for about a year, the Cleveland Clinic is engaged, the CDC started work the day after the Science paper came out, the Whittemore-Peterson Institute has been deluged with calls from pharmaceutical companies and researchers wanting to get a piece of the action but Dr. Mikovits informed us that one big player; in fact probably the MAJOR player in the field is MIA; nothing has been heard from the National Institute of Allergy and Infectious Diseases (NIAID).
    
    The NIAID - there's probably more retroviral experience in the NIAID than in any other organization in the world. The NIAID devoted so much money to, and became so invested in AIDS (some believe over-invested), that it came to be referred to as the 'National Institute of AIDS'.  The agency must simply be swarming with retrovirologists. It and the National Cancer Institute are the two biggest institutes at the NIH with budgets of about $5 billion a year.
    
    Our Former Home - The NIAID was also home to the CFS research program at the NIH until around 2000. Until they kicked us out (or we we kicked them out) the NIAID, in what now appear to be the 'glory' days of CFS research at the NIH, funded three small but busy CFS research centers. Even though NIAID inputs to CFS research over the past 10 years have faded badly the Institute has still easily pumped more money over time into CFS research than any other Institute....but now, according to Dr. Mikovits, its sitting on the fence - a sad, sad coda for an agency that one time was quite important to us and, which should be, if XMRV works out, very important to us in the future. Indeed, if XMRV is found to be a major contributing factor in this disease, it's hard to imagine the CFS program not ending up back at the NIAID at some point.
  
  
  Feb 8th
  
  
  • Dr. Cheney Talks with Dr. Mikovit Live - In TWO days - Check out a live and, surprise, surprise, FREE offering from Dr. Cheney as he presents Dr. Mikovits at the Cheney Clinic on Feb 10th at 1 pm EST (10 am PST) for one hour. Watch it here: It will also be available later on Dr. Cheney's Public Blog  
  • New XMRV Test by VIPDx - VIPDx - the only lab thus far certified by WPI to do XMRV testing - is now (almost) open for business. As we suspected the PCR test is out and a new culture test will be available on Feb 11th.  Prices have not been posted yet but are expected to be significantly lower. In her last lecture Dr. Mikovits stated that everyone who tested negative in the first round of tests will be retested using the new test using samples VIPDx put in storage.  A serology (antibody test) is expected by Spring.
  • Dr. Donnica Moore - new Whittemore-Peterson Institute Celebrity Spokesman - the articulate Dr. Donnica is now the Whittemore-Peterson Institutes official 'Celebrity' Spokesman. Besides her medical credentials she has a son with ME/CFS. She'll help out with awareness and fund raising. Check out the Press Release here.
  • Meanwhile Imperial College - the group that stated XMRV is not in UK CFS patients - announced on Feb 4th that they have developed their own commercial XMRV test providing UK patients with an apparently surefire way of testing negative for XMRV. 
    
    Demonstrating that CDC officials do not take the cake for shooting themselves in the foot in public, Imperial College later claimed the test was not for CFS patients but for prostate cancer patients and then, after shutting the link down, promised to explain on Monday - and then didn't.
  • Dr. Mikovits Comes Through - Dr. Mikovits stated that she answers e-mails and she apparently does - and in a very heartfelt fashion. This is from an email Mark at the Phoenix Rising Forums posted.
    
    "I read your email just after my talk in Santa Barbara and I cried. How to answer. I am so sorry that the tabloids made such a farce of a very real retrovirus infection present in patients throughout the world. We have detected XMRV in dozens of individuals with a ME diagnosis in the UK, Australia, Germany, Scotland...XMRV is NOT a MYTH it is a very real virus that we and others have detected. isolated and sequenced from cancer patients, CFS patients and children!!! Please go to our website www.wpinstitute.org or the Prohealth website to see the entire presentation which describes scientifically all of the differences in the studies and all that we did to show that XMRV is a NEW HUMAN RETROVIRUS of as yet unknown pathogenic potential but significantly associated with both prostate cancer and ME/CFS
    
    There are investigators n the UK who are taking XMRV very seriously and testing by our validated methods and working with us to find out the truth. NOt politics but truth. We will not stop at validation for you, Mark. We will find treatments to give you back whatever health possible. If you send me your contact information, I will make certain that you get tested and if XMRV positive, we will find treatments for you.
    
    6 months from now, I envision thousands of ME/CFS patients enrolled in clinical trials of XMRV therapeutics. The world-wide scientific community knows that XMRV is REAL and the best and brightest world wide are already dedicating their talents to XMRV research!!"
    
    Check out the rest of her email and a discussion on it here.
  
  
  Feb 7th
  
  
  • Dr. Bell XMRV Video's - check out these nice video's from Dr. Bell's latest talk on XMRV. This time the quality is excellent and Dr. Bell has a way of making difficult subjects understandable and he's just good to watch. Thanks to the Baborka Family for flying him out to California, putting on this lecture and recording it.
    
    

    http://vimeo.com/9143012
    
    http://vimeo.com/9254598
    
    http://vimeo.com/9261929    Q&A
    

  
  
  Feb 5th
  
  
  • The First Retrovirus in CFS: Pt II - I came across more information on the search for the first retrovirus in CFS and felt compelled to flesh out the story. It was a fascinating story indeed; full of ups and downs - periods of great excitement and great letdowns. (It certainly made a good book!). This story ends a little differently than does Osler's Web, however. Anyway to check out the big hunt for The First Retrovirus in ME/CFS click here.
  Feb 3rd
  
  
  • Check out an interesting blog on XMRV "All this has happened before"  that examines the British response to the Imperial College study.
  • The CFIDS Association of America reported the American Association of Blood Banking distributed a fact sheet today on XMRV. There's not alot new in this 3 page sheet; it does refer to CFS as myalgic encephalomyelitis at one point - which has gotta be a first for a federal agency. Somewhat humorously (or not) the AABB suggested not to worry about XMRV, if it is infectious through the blood, to get into the blood stream from CFS patients because most CFS patients are too disabled to give blood. Going way out on a limb they said it would be 'prudent' to refuse donations from people who have tested positive for XMRV but will still accept donations from everyone else.
  
  
  Feb 1st.
  
  
  • The Mikovits Prohealth Lecture Slides are now available on the Whittemore-Peterson Institute Site. The forty-one slides present indicated how much information Dr. Mikovits imparted at the lecture. With Dr. Mikovits sticking around and answering questions at length this lecture turned out to be a mammoth presentation indeed; it rang up at 25 written transcribed pages. See below for the transcripts A report from Phoenix Rising will be up 'shortly'.
  • Planning to crash Dr. Mikovits Cornell talk? Please don't - the WPI just informed us that this is graduate and post-graduate level talk in a small room in Cornell; no room for avid ME/CFS patients...but then again we have 25 pages of Dr. Mikovits lecture to digest.
  • Who is this woman?
    
    
  • The CFIDS Association just posted the first photo of Dr. Elizabeth Unger; the acting head of the CDC's CFS Research program (as of Feb 14th). Rather aptly she's reviewing a gene expression microrray.
  
  
  Jan 31th
  
  
  • Dr. Mikovits Talks (Again!) - Dr. Mikovits is continuing to spread the word on XMRV; this time at Cornell University on Feb 5th. Her talk is titled “Detection and Immune Correlates of XMRV Infection in Neuroimmune Disease and Cancer”. Its at Boyce Thompson Auditorium at 12:15pm.
  • The Video's of Dr. Mikovits Stimulating Prohealth Talk at Santa Barbara are up (and transcriptions are coming.)
  • Transcriptions of Dr. Bell's XMRV talk are here: Part I / Part II
  • Transcriptions of Dr. Mikovits talk are up. Part I / Part II / Part III / Part IV / Part V - all thanks to participants of the Phoenix Rising Forums.
  
  Jan 30th
  
  
  • Dr. Reeves Out at the CDC! In a startling announcement at 3pm yesterday the CFIDS Association reported that Dr. Bill Reeves, the head of the CDC's CFS Research program for the past 10 years, was out (as of Feb. 14th) and Dr. Elizabeth Unger, a virologist and cancer specialist would be in charge as the agency looked for a new director.
    
    For more on this and to explore reasons why it may have happened (including an XMRV connection?) click here.
  • A Look Back at Dr. Reeves CFS Research Program - the pro's and con's; check it out here.
  • CFIDS Association Posts Info on the Acting CFS Research Chief, Dr. Elizabeth Unger and on the CDC organizational structure. The CAA reports that Dr. Unger has a solid, solid background in infectious diseases and cancer, is very well published and is currently the Team Leader of the Molecular Pathology program in the CDC. She will not be just the acting director of the CFS Research program she'll be acting director of the entire Chronic Viral Diseases Branch. 
    
    It appears that Dr. Reeves is not alone is his loss of a job; with a massive re-organization going on many positions are probably simply disappearing as different departments merge and new departments are created. It's unclear where and under who's direction the little CFS program will end up. Jeannie Spotila of the CFIDS Association stated it will probably be quite awhile before we know who will be running the CFS Research team.
  • Dr. Bell's hourlong January Lecture on XMRV in Tustin, California presented by the  Barborka Family is up. Dr. Bell just has a gift of explaining difficult topics in a down to earth way. Here he presents his very frank and objective opinion on XMRV to date; its the most exciting thing he's seen in the disease to date and he's waiting to see how it turns out.  I loved how he elucidated how the non-XMRV PCR positive patients in the Science study turned out to be positive (in other ways for the disease). Lots and lots of good stuff in here.

   

  Jan 25th
  
  
  • Dr. Mikovits Speaks - Dr. Mikovits spoke and at length at Prohealth's sponsored talk in Santa Barbara on January 22. Unfortunately the transmission was interrupted early in the talk; it resumed later but I only caught the tail end of it. It was clear, though, that after what appeared to be a couple of down weeks for the WPI's discovery, that Dr. Mikovits enthusiasm was undimmed. One thing we did learn concerned the extraordinary government response to the discovery; Dr. Mikovits stated that the National Cancer Institute has already spent $1 million on it. That's in 3 months....
    
    Compare that to the $500,000 the CDC (begrudgingly) spent on the first retroviral discovery in this illness over about a year and a half span about 17 years ago. What can we attribute to this huge increase in interest and funding for the second major retroviral discovery in ME/CFS? It's not government interest in this disease; the NIH appears to be spending about as much on chronic fatigue syndrome now as it did in 1992 during the first retroviral discovery - a shocking fact given how much we now know about the diseases prevalence and costs. This suggests that the federal bureaucrats that funnel out the money at the CDC and NIH is actually worse than it was then and that government intransigence on the research level is as fixed as ever.
    
    So how to account for all the "CFS-Love" pouring out of the government? Basically we can thank the Whittemore Peterson team for producing a paper that simply could not be ignored. We can thank Dr. Mikovits for taking an interest in the subject and putting her connections at the National Cancer Institute to work and we can thank the Whittemore's for bankrolling what we now know is a very expensive arena in medical research. We can also thank our lucky stars that the WPI found this bug in the blood of 4% of healthy controls; the idea that, post-AIDS, there was an infectious agent floating around in our blood supply was simply too ominous to ignore - even if it came from a paper on chronic fatigue syndrome. For once, ME/CFS patients simply got lucky.
    
    Partial Transcription - Dr. Mikovits talk should be up in a couple days. Until then we have a nice transciption of the first part of her talk by 'TheFreePrisoner" on her blog on the Phoenix Rising Forums (love that tagname!) One thing I liked about her talk was the fact that she really started to walk us through the technical aspects of the study and that's in evidence here.
  
  Jan 19th
  
• • Dr. Mikovits Prohealth Lecture is tomorrow! Prohealth will be streaming live Dr. Mikovits at 2PM PST - that's PST not EST.  This is obviously the talk not to miss. Dr. Mikovits is generally a very enthusiastic speaker; it'll be fascinating to hear what she says after the events of the past couple weeks.
  • Dr. Bell recently talked in California about XMRV. He will reportedly be releasing his own version of the talk but until then Chronic Fatigue Treatments has a blog on it. Its clear that right now we're getting a lot of repackaging of some of the same information. Dr. Bell also recommended that patients not get tested yet. He did note that the cytokine profiles of CFS patients do support the possibility of a retroviral infection but he may have been talking about the Science group since cytokine studies have tended to have rather variable results in ME/CFS. Dr. Klimas 's recently released a study in which one cytokine finding was similar to what was seen in the Science group and another was the direct opposite. This is a heterogeneous group of people.
    
    He also characterized the natural killer cell problems in ME/CFS as being a 'subtle immunodeficiency". NK cell problems are one of the few immune abnormalities that have had really consistent results across studies. Are they important or not? Dr. Peterson appears to believe that they are; according to this report Dr. Bell doesn't seem to believe that they are that significant. (Can anything subtle play a significant role in ME/CFS?)
    
    Dr. Bell also talked about low blood volume - a subject he's been concerned with for many years. He said about 80% of CFS patients have low blood volume but there are no good treatments for it. He believes it may be due to sympathetic nervous system problems.
  • Meanwhile Dr. Klimas is Back on the New York Times - answering questions - not on XMRV - but some very interesting questions indeed and some fuller answers than we've had in the past. She draws some interesting parallels and notes differences between her AIDS and ME/CFS patients. Might AIDS patients be harboring XMRV? Yes, but its probably being knocked down by the retrovirals they're taking. She seems to be a bit less enthusiastic about XMRV right now stating "If — and this is a big if — XMRV turns out to be a big player in C.F.S." but she said little about it so I may be reading something into that.
  
  
  Jan 19th
  
  
  • Dr. Bateman on XMRV and CFS Research on YouTube. If, like me, you for some reason couldn't access the webinar we can thank LuminescentFeeling (from, where else? - the Phoenix Rising Forums) for posting on YouTube. This is particularly gratifying since a technical glitch prevented it from being archived. Check it out here.
  
  
  Jan 17th
  
  
  • With VIP Dx Labs still undergoing updates (three days later) we're still waiting to hear just what's up with the XMRV testing. Is PCR out? Are culture tests 'in'? We'll have to wait further.
  • The First Retrovirus - meanwhile after a fascinating read of Osler's Web I just felt compelled to write something on Elaine DeFreitas hunt for the first retrovirus in chronic fatigue syndrome that ended so badly for her, and really everyone else. My second read of the book really highlighted for me what a complex thing the hunt for a retrovirus can be. The article is too long to post here but you find it on the new ME/CFS Front Page Section of the Forums.
  • The Polls - we've had a few more people respond to the polls. The percent of people testing positive to PCR or culture tests is 50% (n=24). Its still early but thus far how ill you are doesn't seem to play a role in who tests positive. Could the low percentage of positive results for the PCR test be one factor that is causing VIP Dx to pull back on the PCR tests (if they are?) We're at just 26% positive. No one yet has tested positive to the Cooperative Diagnostic PCR poll that looks at different sections of the virus.
  • Don't Forget: the CFIDS Association of America's XMRV webinar with Dr. Bateman starts at 9 AM PST and 12 noon EST. You have to register to watch. Then in 4 days we have Dr. Mikovits on Prohealth.
  
  
  Jan 14
  
  
  
  • WPI updates XMRV Test/Backs Off PCR Test/Defines Relationship between WPI and VIPdx - The WPI is continuing to refine their testing and now has an improved, less costly and more accurate test. This makes sense with what we've heard about testing; some patients tests are sailing right through while others are taking months to get their results. These long waits may be occurring for those getting borderline results thus requiring VIPDx to test them multiple times. Indeed, Dr. Lombardi statement that they considered that one positive hit in multiple tests suggests that some samples are getting multiple tests. This announcement suggests that that may not be as much of a problem anymore. 
    
    Or does it? Its not easy to figure out what's going. Apparently they're using the same culture test. Does this mean the PCR is out? It may. Unfortunately the VIPDx site is down. 
  • Culture In/PCR Out? - The WPI now says that the culture test is "the only scientifically validated methodology to find XMRV".  They state that "At this time no single PCR or whole blood assay alone has been validated as accurately detecting XMRV, and is therefore not an appropriate way to study or diagnose the presence of the virus." This means that your PCR tests, while certainly not meaningless, are not quite diagnostic yet but that the culture tests are - quite a change.
  • This is interesting development to be sure; as has been discussed in this page, XMRV is a new bug whose genetic variation from place to place is unknown; until more is known regarding how XMRV differs from location to location its going to be impossible to create a 'validated' test for it. The DHHS in cooperation with several labs is reportedly doing the work.
    
    Whittemore Peterson Institute and VIPDx Labs - Rumors have been floating around what WPI's relationship to VIP Dx; are they partners? Does WPI own the lab? WPI cleared up some of these questions by stating WPI gets a royalty from VIPDx for each test and that the Whittemore's have 'an interest' in VIPDx that accrues to a trust to benefit WPI. Furthermore, all profits from VIPDx XMRV testing will return to WPI. Their original press release stated that the WPI started 'supporting' VIP Dx after 9/11 interrupted blood sample shipments to Europe, presumably to the ReddLabs which featured RNase L testing. WPI is in discussions with other laboratories inside and outside the US regarding licensing the XMRV test.
  
  
  Jan 13
  
  
  
  • Dr. Mikovits Take the Gloves Off - In an article in RJG.com, an online Reno publication, Dr. Mikovits stated that "You can't claim to replicate a study if you don't do a single thing that we did in our study," which was true since Imperial College's attempt was a validation study and not a replication study. Dr. Mikovits went a considerable step further, however, when she claimed that they actually tried NOT to find XMRV by skewing their experimental design. Just getting started she slammed them for paying to get the study published and suggesting that the insurance companies were behind the study.
    
    Strong words indeed and not often heard from researchers. Unfortunately RJG.com didn't print the details of how Dr. Mikovits felt the study was skewed (patient cohort?, water sample?). The WPI took them to task for not replicating the orginal study but its clear that they feel the group didn't do the validation part correctly either; ie if XMRV was there they don't believe they would have found it.
    
    It's unfortunate indeed that the first 'replication' attempt was from such a suspect source. While Dr. Mikovits pointed out how anxious the Imperial College finding had made patients, aside from that, this brouhaha will notmake any difference as the studies from different groups and with different patients come flooding in. Finding out what's up with this newly discovered bug will take time and study.
    
    Annette Whittemore calmed things down a bit when she stated that We think XMRV is, at the very least, a biomarker for a subset of patients with Chronic Fatigue Syndrome." which is a good safe statement to make. 'XMRV', whether or not it causes ME/CFS, would make a great biomarker because it appears to be rarely found elsewhere but is found in at least a significant percentage of CFS patients. Researchers have been looking for a biomarker like that for over 25 years and have turned up nothing.
  • Imperial College Responds - Meanwhile Dr. Cleare responded to questions about the patient cohort in the Imperial College Study. He asserted that the patients in the study were much like patients everywhere; they all met the standard (Fukuda) definition, most experienced physical and mental fatigue, most experience post-exertional malaise. They exclude most psychiatric disorders including somatisaton -which they say is rare anyway. Nor did they try to 'shape' or 'select' the patients appearing in the Imperial College study. Nor is this group more 'psychiatric' than other groups and, in fact, they resent the implication that they are.
    
    As a laymen, it seems highly, highly unlikely to me that a different cohort could account for the results of the Imperial College study.
  
  Jan 12th
  
  
  
  • Dr. Bateman in CFIDS Association Webinar - This is the internet in action! Sign for this webinar put on by the CFIDS Association and you can watch Dr. Bateman speak on the XMRV with Dr. Suzanne Vernon moderating from the comfort of your computer. Congratulations to both the CFIDS Association and Prohealth for creating two live web events. First comes Dr. Bateman on the 18th and Dr. Mikovits (via Prohealth) on the 22nd. Register for the CAA's presentation here. and Prohealths Presentation here.
  • Gordon Medical Associates is a medical group that's been working with the Whittemore Peterson Institute on XMRV. They just sent us a little update which again suggests that the testing side has hit a few bumps. Dr. Lombardi recently stated that the viral copies of the virus were very low and that the testing process was quite slow. Gordon Associates first called for a bit more patience and then stated that XMRV is being a bit 'difficult'.
    
    

    "First, those GMA patients who were tested in either one of two studies need to stay patient a little longer. We have provided over 130 samples to Dr. Judy Mikovits for extended testing for XMRV. Dr. Mikovits tells us most of those samples have been tested, and that we will receive the results as soon as they are finished analyzing the data. Those who provided samples to Panorama labs will also need to wait. XMRV is proving to be a difficult virus to find in testing, and both labs are working to do their best to provide accurate information."

    
    
    
  
  
  Jan 11th
  
  
  • Dr. Bell Speaking in Santa Ana, Ca on XMRV January 15th
  • Cooperative Diagnostics Results Top VIPDx Results - Neither poll is anything to cheer about regarding participation but it's remarkable that we now have more results from the CD PCR poll (13) than the VIP Dx PCR poll (11). (The combines VIP DX PCR/Culture Poll is still tops with 16 results). Given that the WPI and Dr. Coffin both thrashed the Cooperative test when it first came it this can only suggest that VIP Dx Labs is moving very, very slowly.
    
    Meanwhile no one has tested positive for Cooperatives two gene sequence PCR test and only 18% are testing positive for VIP Dx's one gene sequence PCR test. (66% of patients in the Science paper tested positive.) Fifty percent of patients are testing positive, however, for either a PCR or the culture test which is a bit higher than the 36% rate reported by Glean in his article. 
  • My Cooperative Diagnostics Test - I received my test result back from Cooperative Diagnostics. I was, like everyone else who has taken the poll thus far, tested negative. I was able to get the test done because I was part of an XMRV study CD is doing. 
    
    Given the results of the Imperial College tests the results are illuminating because both groups appear to be using a similar strategy; ignoring the sequences the WPI tested for and instead focusing on sequences they know (or believe they know) are there. This is certainly a legitimate way to test for 'XMRV' as we know it. Whether its a good test for what the WPI found is another question. 
    
    This is what they said. 
    
    
    The two strains of XMRV found by Lombardi et al in chronic fatigue syndrome that were sequenced had roughly 6 bases that were different from prostate cancer XMRV. We used these strains in addition to prostate cancer strains and several strains of murine leukemia viruses (MLV) in the design of our test. In contrast to published tests for XMRV that have been designed in highly variable DNA regions in the MLV family ... we chose to design our initial test to use the pol gene so it could detect all MLV species, including XMRV. This means we tested a DNA sequence that has not changed in hundreds or even thousands of years on an evolutionary scale in the MLV family. This test would be more apt to detect XMRV than any other test used. Therefore, we would likely have more positives than previously reported in PCR tets for CFS when XMRV is actually present.
    
    We also used a superior test sensitivity, enabling the detection of 10 to 25 times few viruses in a blood sample than previously reported tests for XMRV. This was proven when we were able to detect XMRV in 1 infected 22Rv1 cell from a commercially available prostate cancer cell line in a background of 2.5 ug of extracted DNA from blood. We also designed a second test with the same performance characteristics of the first. This allowed us to also evaluate the env genes, creating an extra confirmation step in our testing.
    A Laymen's Assessment of the XMRV Situation (Laymen in Charge - Be Very Wary)
  • REPLICATION VS VALIDATION STUDIES - the Imperial College and CD tests are validation 'studies' not replication studies and there's a big difference between them. Replication studies follow the first studies techniques to the letter.They're using the same processes to find the same genetic sequences that the original study found. 
    
    Validation studies, on the other hand, simply try to validate the first studies assertion - in this case the WPI's assertion that they found XMRV. They're not trying to replicate the original techniques; in fact, it's better if they don't. Virus hunters can use any number of techniques to find a virus; if a virus is there any of these techniques should be able to find it. Thus, they're often using different kinds of PCR tests and are often looking for different genetic sequences than in the original study. When Imperial College or CD attempts to detect the virus using a different means than the WPI does, its trying to validate their assertion that they've found XMRV - not find the same genetic sequences WPI did. 
    
    The WPI's Variable Genetic Sequences - It's intriguing that CD states that the tests thus far developed for XMRV focused on 'highly variable' regions of the DNA (we heard this from another researcher). The WPI tested 'gag' sequences which, as I remember, are from the coat of the virus. Since this part of the virus is constantly interacting with the environment it's not surprising that it might be variable. 
    
    Cooperative Diagnostics states, though, that ALL XMRV tests, not just the WPI test, have focused on variable regions of the genome. The upside to that approach appears to be that these tests can differentiate between different types of murine retroviruses; ie they can pick out XMRV from other murine retroviruses. The downside is that because they are variable they could conceivably differ from strain to strain and patient to patient - thus some patients could test negative when they're actually positive.
    
    Cooperative Diagnostics Conservative Search for XMRV - Cooperative Diagnostics is taking a very conservative approach by focusing on highly stable regions which are shared with other retroviruses. These were gene sequences in the pol gene that are believed to have been stable for 'hundreds or even thousands' of years. Since several viruses share these regions they expected higher levels of false positives ; ie if anyone carried those viruses they would show as testing positive for 'XMRV'.
    
    Highly Sensitive - They also developed the most highly sensitive test yet. They demonstrated the test was able to identify even very low levels of the XMRV virus found in standard preparations of prostate cancer cells. 
    
    Two Genetic Sequences - They also looked at at the env gene sequence found in the XMRV. This is the sequence that the Cleveland Clinic - in small number of samples - demonstrated was in the WPI samples - and helped convince them the WPI had found XMRV. Because Cooperative Diagnostics is looking two stable sequences they appear to be providing the most comprehensive test for XMRV commercially available.
    
    At least in my sample and the 12 other people who voted in the poll none of us tested positive for these sequences; ie we did not have XMRV. 
    
    NOT XMRV? - eaving aside different patient cohorts, geographical locations, and other confounding factors the Imperial College and CD findings thus far refute the WPI's claims that they found XMRV. Instead they suggest either that the WPI found a different type of XMRV or some gene sequences that are similar to those found in XMRV but not the actual bug itself. 
    
    The Weak Link? - it could be that XMRV is more variable than researchers know; that they're looking for gene sequences that are slightly different than the standard XMRV sequence. That standard XMRV sample, after all, must have come from prostate cancer studies from a small probably localized set of patients and may not reflect what XMRV looks like in the rest of the population. The problem with this argument is that Cooperative Diagnostics tried to account for this by looking for a genetic sequence that they don't believe changes between several viruses alone within a virus - and didn't find it. 
    
    Contamination? - Its also possible that the WPI is picking up an endogenous retrovirus that has some similar genetic sequences to XMRV. This is the 'contamination' theory which no one really seems to take seriously. For one thing the WPI fully sequenced two samples of XMRV and parts of third and they had very close genetic similarity to XMRV
  
  
  The BATTLE
  • Evidence For the WPI's Assertion: they identified a 'gag' sequence that appeared to come from XMRV. The Cleveland clinic confirmed that seven of 11 patients also had an 'env' sequence. Importantly, the WPI sequenced 2 1/2 strains of the bug from their patients and it turned out to be XMRV. The weak point here was that the 'gag' sequence is variable in XMRV but they have that full sequencing of strains to back them up - strong evidence in their favor. Plus while it's not evidence for XMRV the WPI did find something that was able, to jump from an infected cell to an uninfected cell in a culture test; this doesn't appear to be a fragment of something - it appears to be 'something'. 
    
    Evidence Against the WPI's Assertion: One study and the poll results from another labs test that looked for very stable genetic sequences in XMRV have not found them; ie no XMRV. Since they haven't found any XMRV it's clear that patient cohorts are not the complete answer. 
    
    A Conundrum - There doesn't appear to be any good answer - we're at a conundrum. Short of someone having made a technical error its hard for this layman to understand these conflicting results. Perhaps the best way to leave it is that XMRV is a newly discovered retrovirus and much remains to be learned about it.
  Jan 10th
• The XMRV Quiz is up! Have some fun. Check out the new XMRV quiz on Phoenix Rising here.

 Jan 9th



• VIPDx - An enterprising member of the Phoenix Rising Forums asked VIPDx some questions about their tests and they answered right back. When asked about that rather low 36% positive rate VIPDx replied
  
  

  When Whittemore Peterson did their research it was on a small group of patients who have a “confirmed diagnosis” of CFS.
  
  VIP Dx is testing hundreds of patients whose medical history is unknown and a diagnosis of CFS may or may not be confirmed.
  
  Although we strive to offer the most sensitive test available XMRV is typically present at a very low-copy number and may be below the limit of detection from time to time.
  
  Retroviruses (like XMRV) are integrated into cellular DNA and are considered life-long infections; it is possible that the immune system may decrease the virus to a level below the limit of detection from time to time (non-symptomatic). Presently, the life cycle of the virus is unknown; if you receive a positive result at any point, we do not recommend re-testing.
  
  XMRV testing at VIP Dx uses the same methods as published in the Lombardi, et al, October 2009 issue of Science. This test included PCR testing on lymphocytes as well as virus culture. This method requires 20mL of whole blood and although it is much more time consuming and labor intensive than other methods, we find that it dramatically reduces the rate of false negative results. It is also why the cost of this test is greater than that of tour standard PCR tests.&

  
  
  Thus there are potentially two reasons for the lower than expected (but still significant) rate of positive results (a) different patients (b) the virus could actually be there but in numbers so low that its difficult to find at any one time. One  member of the forums sent his blood in in Nov and still has not gotten a result. On the other hand a few people who have sent their tests in got their results back fairly quickly. It sounds like there are some borderline results that VIP Dx is being careful with; which is good to hear but also suggests they haven't nailed the test down completely yet. (?)

 Jan 8th


• Biff! Bam! Boom! - the Economist weighs in with characteristically fun to read article that actually brings up some potential problems with the study.
• Dr. Donnica is back! Check out our best spokeswoman for this disease on a video she did for the Doctor's Channel where Doctor's talk to Doctor's. This is short general introduction to CFS (no XMRV) but it's nice to see. She gets MCS in there.
• Dr. Enlander Talks! - Dr. Enlander also did a very short video for the Dr's channel.  Its great to see ME/CFS specialists talking to Doctors about this disease (instead of CDC personnel). Dr. Enlander gets myalgic encephalomyelitis in his short talk. No XMRV here either but you've got to think the interest in XMRV is sparking more interest in this disease in general. Dr. Enlander will have a talk on XMRV coming out.

Jan 7th



• Imperial Study Fallout: Day Three - there's nothing like a failed replication replication attempt to get the information flowing. Sam Kean of ScienceNow reported that after questioning why the Imperial Lab didn't look at the same genetic sequence, Dr. Lombardi stated that after 300 tests (only 300 in a month plus?)VIPDx is getting a 36% positive rate - about half found in this study and far fewer than the 95% reported after the study. Meanwhile VIPDx Labs is getting some heat for offering a $650 test that (a) has not been standardized and (b)for a bug whose effects are clearly unknown.
  
  Dr. Coffin, one of the top retrovirologists in the nation, suggested that both groups could be correct and this seems to make the most sense at this point. Some research groups are choosing not to use the genetic sequences in the WPI test because, at least according to one source, they come from a more variable region of the genome. Instead they're looking for genetic sequences that they know are stable in the virus. XMRV is, however, a new virus which has not been well studied. Although XMRV's genetic variation in the US appears, at least at this point, to be quite low its possible that the genetic sequences outside the US are different. If this is so then a probe using those sequences wouldn't pick up any evidence of the virus.

Jan 6th



And if you see some negative papers coming out, don’t be discouraged. It’s going to happen. There are going to be some negative papers. People really jump to do this. And the method is not that easy and getting the right bits and pieces you need together  (is not easy)" Dr. Nancy Klimas





•  Whittemore-Peterson-Institute Responds - The WPI iweighed in the next day and in very blunt language took the Imperial College study to task calling it 'meaningless'.  Besides the different patient cohorts and different blood sampling procedures they cited
  
  
  • the use of a water control rather than a blood control
  • different primer sequences and amplification protocol which was not validated by a clinical control
  • fewer rigorous tests of accuracy
   If I understand them correctly they're also assert that the group should have used an positive sample from a patient rather than a standard XMRV sample as a control. Plus they did more tests involving three different labs to ensure accuracy than the Imperial College group.  Plus they had questions regarding the different protocols.
  
  Its getting pretty muddy here. One thing we're going to see are studies replicating their results against standardized XMRV samples (eg Imperial College) or against positive samples from the WPI. Theoretically, if both samples contain XMRV they should produce similar results but if the 'XMRV' in them is slightly different it could create problems. 
  
  There are differences of opinion regarding how exact a lab needs to be in replicating another labs results. There are several different PCR techniques and variations within each kind of technique. Some researchers assert that any valid technique should yield positive results. Others believe slight differences can make big differences. At this step of the game - with such a new finding - it seems pretty clear that the first priority is exactly duplicating the original study's findings.
• The Brits Smack XMRV or Do They? - Attempting to stop the bleeding in the media which appears not to be paying attention to any of the possible problems in the UK study the CFIDS Association of America produced a press release that stated in no uncertain terms their concerns about "many elements" of the study including the rush to publication (three days between submission and acceptance), the different processes used in the two studies and the differing patient groups.
  
  Dr. Suzanne Vernon, the CFID's Associations Scientific Director produced the critique of the study and the CAA touted her credentials in Press Release; a directorate in Virology and 17 years years of public health research on infectious diseases.
  
  Dr. Vernon closed the press release alluding to a need for a 'standardized test' before millions of dollars of funding are potentially wasted. Developing a standardized test requires having multiple labs test and retest different procedures until they all agree they have found the correct test. Only then will it be possible to determine the true prevalence of XMRV.
  
  Gird Your Loins ME/CFS Patients - in the meantime Dr. McClure's comments suggest we may be about see a stream of similar findings. A participant in the Phoenix Rising forums reports a CDC report will be out next week. Now is the time to member both Dr. Klimas and Dr. Vernon's admonitions to sit tight and not take any one (or two) results too seriously at this point.
  
  Meanwhile the WPI remains silent but are reportedly working on their response. 
• The Differences in This Study - How did this study differ from the Science study?
  
  Its Location - the disconnect between researchers ability to find XMRV in the US and Europe is growing; both attempts to replicate XMRV findings outside of the US have failed; both a large German study prostate cancer and this large UK study found zero evidence of XMRV. Is this due to differences in XMRV prevalence or to differing laboratory procedures? Patients report that Dr. Mikovits stated there may be significant geographical differences in prevalence in the US;- some regions reportedly had much rates of infected CFS patients than others in their testing. XMRV has, reportedly, been found in Europe, however, and its hard to imagine that the geographic differences could be that distinct. Laymen's assessment  - if its a problem its not THE problem.
  
  Different Gene Sequences - The Imperial College Group did not search for the same sequences as did the WPI. They may be following a somewhat similar technique to the Cooperative Diagnostics Lab. Cooperative Diagnostics reported that the WPI looked at genetic sequences that contain high variability. Because of this they searched for genetic sequences that have been stable for long periods of time. It's possible the Imperial College group used the same rationale. Laymen's assessment - possibly a key issue
  
  Blinded Study - the Imperial College Study was 'blinded', albeit in a strange way. Although the PCR technician didn't know which samples he/she was assessing all the samples came from CFS patients or 'water controls'. Although the WPI study contained healthy controls it was, apparently, not blinded. Laymen's assessment - not a huge issue; differing percentages of positive patients could be attributed to operator error - but not to such huge differences.
  
  Different Procedures - Dr. Vernon has noted that several techniques were different in the two studies. Some researchers will argue that techniques don't have to be replicated exactly for a robust finding to show up. Others argue they do need to be replicated exactly. Inexact replication of the first retroviral finding was a major controversy of the first retroviral finding in ME/CFS and experts differed on whether it mattered or not. Laymen's assessment - potentially a major issue.
  
  Different Patient Groups - the Imperial College group used quite ill patients who met the CDC criteria judged (by the investigators)to be 'typical' of chronic fatigue syndrome patients in Australia and the US. Its possible that the WPI group (immunologically challenged with metabolic dysfunction) were a different subset. However, in a large group of CFS patients (168), surely a good portion would fit the WPI profile, and no patients at all tested positive. Laymen's assessment - if its an its not THE issue.
  
  Laymen's Overall Assessment - This is a methodological problem rooted in the complexities of PCR analysis.  (Any PCR experts outs there?)

Jan 5th


• First XMRV Replication Study Published - and its a doozy. Originating from the Imperial College and with patients supplied by Simon Wessely, the study found zero (that's zero!) evidence of XMRV in 186 CFS patients. Here's a link to an article by the BBC and a link to the original paper
  
  The basics of the study were that they looked at a lot of patients (186) who were quite ill (only 19% working), had high rates of disability, about 50% of which had infectious onset. They all met the standard CFS Criteria (1994 Fukuda) and they did not have a major psychiatric condition. (I'm unclear if depression is excluded or not). The researchers did not test healthy controls.  They had a positive sample of XMRV to ensure that they could find the virus.
  
  Remarkably, they didn't find the virus in any of the samples - a similar finding to an earlier German study that failed to find XMRV in any prostate cancer samples. These studies underline how complex situation these efforts are. Earlier the CFIDS Association noted that the German study did not adequately replicate the original XMRV prostate cancer study. Now Dr. Vernon of the CFIDS Association asserts the same is true with this Imperial College study.
  
  In a CFIDS Link report Dr. Vernon stated that this study 'should not be considered a valid attempt to replicate the findings" of the Science Study. Basically she listed a series of methodological questions that could have interferred with the Imperial College Researchers ability to find the virus. Most of these will fly right over most of our heads but they include:
  
  
  • collecting the virus in different kinds of collection tubes
  • the DNA from the patients was extracted and purified in a different manner
    
  • they used different amounts of DNA to amplify their assays
  • they looked at different parts of the genome
  • tthey ran the PCR under different conditions
  
  Based on Dr. Vernon's experience  working with PCR any of these could have affected the results. She didn't say that they did but that they could have. She then pointed to a larger much more rigorous study that the Department of Health and Human Services is engaged in. (Both Dr. Vernon and Dr. Mikovits are part of a team overseeing that study). Since that study will involve multiple laboratories coming up with a standardized test first that study will take longer to finish. She did say that the CFIDS Association is urging that the DHHS study is completed as expeditiously as possible. She, also, like Dr. Klimas urged patients to be prepared for conflicting results'
  
  "The U.S. Department of Health and Human Services Blood XMRV Scientific Research Working Group is conducting a rigorous study to detect XMRV. Multiple laboratories will standardize methods to optimize sensitive detection of XMRV proviral DNA and viral RNA and then, once methods are standardized, these same laboratories will test coded panels of blood samples obtained from healthy blood donors and CFS patients. We look forward to the results of this study and urge that it be completed expeditiously, especially in light of this report from the U.K. In the meantime, be prepared to read about more studies with conflicting findings. Rather than simply accept or dismiss new information, we will help make sense of why discrepant results occur."
  
  It sounds like this study will most likely be the gold standard for XMRV study. It may, is more than any other study, be the one that validates does not validate the Whittemore Peterson Institute's findings.



 Jan 4th

 

• Dr. Mikovits will be giving a 2 hour presentation on XMRV in Santa Barbara on Jan 22nd. Tickets are still available. Prohealth will also be streaming live the presentation but definitely get there if you can. My experience with Dr. Mikovits is that she's very approachable and she's happy to answer questions before or after a presentation.

Dec 30th


• CFIDS Association of America reports that the XMRV discovery makes Discover magazines list of top 100 scientific discoveries of 2009
• A short article on XMRV had Annette Whittemore stating, rather positively, that “We’re very hopeful that within the year, we will begin to see clinical drug trials for XMRV-related diseases such as Chronic Fatigue Syndrome, fibromyalgia and many other unknown diseases" 
  
  Nothing the WPI has seen in their labs over the last couple of months since the Science article came out  has compelled them to pull back on their expectations at all. Particularly intriguing is Annette's statements about 'many other unknown' diseases. Does she mean poorly understood diseases like MCS or IBS? Or is she referring to neurological disorders that simply haven't been described adequately yet? Diagnosing brain disorders can be very sketchy; patients often don't fit into the standard 'autism' or 'multiple sclerosis' profile - there's alot of drift in there. Is Annette talking about a new group of XAND (XMRV Associated Neurological Disorders?).
  
  The WPI is clearly engaged with many groups spread across the US and Europe with Annette stating “We are continuing to work with the National Cancer Institute and many other individual researchers,” Whittemore said. “We also are doing confirmation studies of additional Chronic Fatigue Syndrome patients with other countries, including Sweden, Norway and the United Kingdom, as well as many scientists across the United States.”
• Cooperative Diagnostics Lab and VIPDx Polls Show Divergence - We still have an almost inexplicably low number of people participating in the XMRV Testing Polls but even so we have a divergence in the results for the PCR tests. Thus far 30% of 10 people have tested positive for the PCF test from the VIPDx lab but nobody yet has tested positive (8 results) to the Cooperative Diagnostics poll. As Nancy Klimas pointed out we should expect divergent test results until a standard test has been developed.
• XMRV Media Thread on Phoenix Rising - We've had quite a lull in XMRV news so perhaps its a good time to check out of my favorite features in the XMRV section of the Phoenix Rising Forums. Summer created a media section that contains short excerpts and/or links to media articles on XMRV. Thus far over 80 posts have been made.
  
  In this one From Women's Day Dr. Mikovits states people might want to put off being tested for now since there are no good treatments for some XMRV yet. She also says that treatment trials at the Whittemore Peterson Institute could start as early next year.
  
  There's also this YouTube video from Imogen Heap on XMRV . There's lots of stuff on the Media Page. If you want to look back at what's happened or if you want to see you might've missed check out the mighty there might Media Thread Summer put together.
• Faces of XMRV - IslandFinn also started an XMRV images thread that has some fascinating images.

 Dec 24th
 



• Dr. Bell's Latest On XMRV - One section from Dr. Bell's December Lyndonville Newsletter is worth quoting in full because it is so timely. XMRV studies will at some point start pouring out.  Both Dr. Klimas and Dr. Bell have stated that the important thing, particularly in the early stages, is not to over-react to negative or even positive reports. As Dr. Bell explains the process is more complex than we know and that it will take some time before we know what's  really what.
  
   "...Not surprisingly, the first stage of the attempt to replicate these results has resulted in various international groups almost entering a race to see who could replicate or refute the WPI results first. And this has meant they have gone for an easy and immediate source of patient material - stored blood samples. I am not aware of any stored blood samples here in the UK that are from patients who meet Fukuda plus Canadian criteria and I doubt if there are any."
  
  This brings up really important issues in interpreting the results of studies that will come out over the next six months. In my practice over the years, I have seen the whole range of patients from kind-of tired to bedridden orthostatic intolerance. Despite what the different criteria attempt to prevent, much of the diagnosis is based upon using the "force". There are some clinicians who diagnose CFS and I have absolutely no idea of what their patients are like. Through years of observation, I do have a concept of what Dan Peterson's patients are like.
  
  So is XMRV in really severe ME? CFS? Orthostatic intolerance? CFS plus POTS? Mild fibromalgia? Atypical MS? CFS with or without depression? Chronic Lyme disease? Multiple chemical sensitivities? And what about stored samples? Samples taken in EDTA or heparin? And so on.
  
  So what does this mean? It means that if someone can't find XMRV in a study, it is either because it is not in the patients they tested, or their lab could not detect it even if it was there. Or the strain might be different, or they used the wrong tubes, or the diagnosis was wrong. And on and on. Again using the "force", I would not be surprised if some of the quickest replication studies fail to confirm XMRV. But as long as people do not jump to conclusions too quickly, science will win out. Truth will win out. That’s all I am looking for."
  
  Interestingly, Dr. Bell felt that the Dubbo studies would be a fantastic test for XMRV. Since these studies examined people as they came down with CFS (or not) following an infection if XMRV was found in those who came down with CFS but not in those who did not following the infection it make a strong case that an XMRV infection somehow primes people for a descent into CFS once they get another infection.
  
  As you may remember, a small percentage of persons developed ME/CFS after Epstein-Barr virus, Ross River virus or Q fever. They must have saved blood from those who came down with ME/CFS and those who did not. Test the blood for XMRV. If it is in the ones who came down with ME/CFS, but not present in the blood of those people who had regular mononucleosis and quickly recovered, we would have the answer. Ah…if only it were that simple…
  
  A patient has reported that Dr. Lloyd's XMRV study of the Dubbo patients will be released in January. (See below)
• XMRV Study Page - The studies are adding up. We're up to fifteen studies/groups focusing on XMRV and we may have identified our first release; Dr. Lloyd of the Dubbo studies in Australia is reportedly releasing his results in January, 2010

Dec 23rd



• XMRV Global Action Advocacy Group Forms - Participants in the Phoenix Rising Forums just started the XMRV Global Action Group to 'accelerate global access to diagnostics, clinical trials, treatment and prevention for diseases associated with the retrovirus XMRV" Check out their Facebook site.
• DiagnoseSupport is focusing on getting the word out internationallly about XMRV Section and are providing translations, etc. They've joined with the XMRV Global Action group.

Dec 21st



• The Autism-XMRV Connection - Dr. Insell, called the 'nations top research coordinator', expressed real interest in the XMRV autism connection. Not long after the publication of the Science paper Dr Mikovits reported that 40% of a small group of autism patients tested were positive for XMRV. Dr. Insell is taking a real interest in XMRV, stating
  
  "We are hot on that, and I wish I could tell you more," Insel said. "All I can tell you is that we have an intramural program here which is kind of our home team, which has seen about 400 kids with autism over the last couple of years. And they have been looking at regression; they've been looking at recovery." He said the researchers "jumped on the XMRV thing even before it was published."
   
  Dr. Insel said that he had heard that researchers at the University of Nevada had identified XMRV in about 40% of ASD children studied. "I have been trying to track that," he said. "There is a paper that has been submitted, but I haven't been able to get it, and I don't know what the data look like. But I think this is really interesting."
   
  Why? Because, he said, "If we could just find a small group, and the opportunity to begin an antiretroviral treatment regime, that could be terrific. That would be the kind of thing we're really looking for in this field, is finding the subgroups that might have specific therapies that would make a difference."
• Whittemore Peterson Institute and the Friends of the Whittemore Peterson Institute - there are two Facebook sites on the WPI. The Whittemore-Peterson Institute Facebook site is the official WPI Facebook site. You can find the WPI's latest releases on XMRV and other subjects relating to ME/CFS there. The Friends of the WPI  has been a site for people interested in XMRV and the WPI to gather and discuss the Institute and its findings. The WPI will eventually eventually close that site and is asking everyone to move to the WPI Facebook site.
  
  Annette Whittemnore penned a Letter from the Whittemore Peterson Institute on December 19 outlining what Institute has been up to and  the impact its made.

Dec 18th



• The XMRV Polls on Phoenix Rising - The results are slowly trickling in with just 12 people thus far taking both the PCR and the Culture tests. Of these 50% tested negative to both tests and only 25% tested positive for an active (PCR) infection.  On the other hand regard to the separate Culture test - which test to see if XMRV is present in the cells about two thirds of the people have tested positive.
  
  That "Latent'  Virus- My understanding is that researchers refer to viruses that are not traveling in the bloodstream and infecting other cells as 'latent' but  that they are discovering that 'latent' is a decidedly poor choice of words as these viruses can be quite active in the cells they're found in. Since XMRV appears to be found them immune cells it could be disrupting their function - latent does not necessarily mean not significant. It does mean the virus does not appear to be actively spreading in the body.
  
  Having a negative test result may or may not be positive event depending on how you view the situation. Check out how a member of the Phoenix Rising Forums is dealing with her surprise at her negative result.
  
  Both Dr. Klimas and Dr. Bateman and, in fact, the Cooperative Diagnostics Lab - suggest patients not get tested until we have a standardized, independently validated test. This doesn't mean the VPI Dx test is not good - it was clearly good enough to get into one the most prestigious journals in the world - but that it's probably not perfected; that is while most of the people taking it will get an accurate result there will be some people, probably only a few, who may not. That's my understanding. A standardized test paid for by insurance may be ready in six months.
• More From Dr. Klimas  - Dr.Klimas cautioned everybody not to get too excited if some negative studies pop up - she expected to see studies with highly positive and highly negative  results show up and everything in between. She noted that she's been contacted by several researchers who want access to her samples but she's been very careful. Because researchers use a variety of different methods to look for viruses - and methods to make all the difference - she's focusing on what methods they're using.
  
  It sounds like we should be ready for a rather turbulent period! Enough attention has been focused on this virus, though, that Dr. Klimas seems fairly positive that the research community will get to the bottom of what's going on; ie. we won't be left with lingering questions as we were after the DeFreitas retroviral finding in the early 1990's.

 

Dec 16th


• Dr. Bateman's Lecture on XMRV - this is almost an embarrasment of riches. A video of Dr. Bateman's recent 1 1/2 hour lecture on XMRV has just been posted online. Dr. Bateman is one of most active physicians serving on the CFSAC and IACFS/ME. She runs the OFFER group in Salt Lake City and is well acquainted with Dr. Peterson's work. She is another professional who came to ME/CFS the hard way - her sister died of CFS. (While you're there check out OFFER's large selection of video presentations). Like Dr. Klimas Dr. Bateman is an ace at presenting scientific information in a clear, understandable manner. She was more cautionary than Dr. Klimas regarding XMRV.
  
  Inheriting XMRV? - Both she and Dr. Klimas talk about the possibility that you could've inherited this virus! Its clear that mice pass this virus down in their genome from generation to generation. Do humans as well? No one knows but its definitely a possibility. (You can see why the retroviral community is so interested in this virus - its an interesting virus! Like HIV its a retrovirus but its like the UN-HIV otherwise; its possibly inherited, its not replicating much, and it doesn't mutate much - its like the other side of the retroviral community just showed up in humans and the researchers would love to get their hands on it.  Dr. Bateman noted that its gotten very little study thus far - thats clearly changed.)
  
  
That Special Cohort? - Dr. Bateman emphasized how ill the patients in the Science study were and that its unclear how the findings will translate to more typical patients. She noted that the tests to identify haveXMRV are "new, imperfect, (and) not standardized" and rattled off a stream of difficulties associated with PCR, antibody and culture tests; testing is very new and its evolving.

Treatment - Just as Dr. Klimas does Dr. Bateman emphasized how toxic many HIV drugs are; she noted they were developed to save the lives of people who were dying and that the medical community was willing to tradeoff a high degree of toxicity for saving lives. They can cause a pain disorder (peripheral neuropathy), 'drop your blood counts', give you diabetes, etc. The pharmaceutical community is definitely interested; they are already moving into animal testing and Dr. Bateman has already been approached about being part of clinical trial network.

The mouse - human connection - We know XMRV came from mice - but when did it jump to humans? Several researchers have suggested that it was fairly recent but Dr. Bateman noted that XMRV has probably been in mice for millions of years! Like Dr. Klimas Dr. Bateman noted that sexual transmission does not appear likely - given the epidemiology of CFS (few husband/wife pairs).

Testing - Dr. Bateman mirrored Dr. Klimas' suggestion regarding testing - she advised patients not to get to tested yet. Enough interest has been generated in the research community that it won't be long for a test that's been independently validated and standardized to appear. You could falsely test positive or falsely test positive. She also noted that there's no treatment for XMRV yet. She also believes the study results will run the gamut: from almost no patients having the virus to most patients having the virus depending on what types of patients are in the study to what kinds of tests they used.

The Autism Connection - the WPI didn't just look at any autism patients, they looked at flu-like onset autism- these were the patients they found XMRV in.

Dr. Bateman is VERY excited about the XMRV finding- what is looking forward to right now is more clarity about it -  which will simply take some time.

Dec 15th

• The WPI has a new partner (and we have a new study) The distinguished Cornell University in upstate New York has just posted a job offering for a postdoc for study on XMRV in ME/CFS. Both the WPI and the Columbia University Center for Infection and Immunity are partners. (thanks to Parvofighter for the tip)
• The XMRV studies keep adding up and now Phoenix Rising has a page specifically devoted to them.
• Dr. Klimas' lecture - meanwhile more interesting stuff from Dr. Klimas' XMRV lecture. She does not recommend a test right now; for one the tests are still being tweaked - you could get a false positive or negative and for two - there's really nothing you can do about a positive result right now; most HIV drugs are just too nasty for ME/CFS patients - as she said 'you guys are fragile' (more fragile apparently that AIDS patients (!).
  
  
While its not a cure Dr. Klimas has also, like many doctors, found that cognitive-behavioral therapy is very helpful for improving ones quality of life and getting their symptoms under control.

She likes Omega 3 fatty acids (4 grams!), COQ10 (look at 120mgs), Isoprinosine (over the counter Inosine) and Xyrem for sleep. (Each has a section on the website)

Congratulations, again to PANDORA and the CFSKnowledgeCenter for the wonderful job they did taping this long presentation, editing it and getting it online.



Dec 14th




• Dr. Klimas on XMRV - Transcriptions of Her Lecture - Part I and Part II
  
  Dr. Klimas is giving us new insights into XMRV. Some highlights for me thus far: the WPI researchers actually found XMRV in virtually every ME/CFS patient in their study; about 2/3rds of them had an active infection but 30/33 patients without an active infection were found to have a latent infection; that is, the virus was found in their cells.
  
  Dr. Klimas is also very clear that this virus is causing the natural killer (NK) cell and T-cell dysfunction found in this disease. The NK cell dysfunction is pretty significant since NK cell problems have been consistently found in ME/CFS and I'm not aware they are connected with other diseases. So XMRV provides a very nice tie-in with a particular abnormality in ME/CFS.
  
  She also reported that drug companies have literally thousands of compounds sitting on their shelves that didn't make it to the HIV market but could possibly work for XMRV.
  
  Ampligen? Ampligen is a possibility - for some patients. Dr. Peterson has found that it appears helpful in the lab in some patients and not in others.
  
  

Dec 13thzDate">Dec 13th



• Dr. Klimas's Big Talk on XMRV - ME/CFSCommunity has just released Dr. Klimas's 2 hour plus talk on XMRV in mid-November on video. Dr. Klimas has the ability to present complex issues in understandable ways. Check it out in ME/CFS Community's extraordinary Video Center!

Dec 12th



• Dr. Bell Talks! - The Daily News, a western New York newspaper had a short piece on Dr. Bell's talk on XMRV. What did we learn? Dr. Bell expects that we'll see at least a half a dozen research papers on XMRV over the next six or seven months. With regards to treatment Dr. Bell noted that "There are pharmaceuticals on the market that can kill XMRV in a test tube but there are no conclusive studies done to determine their efficacy on humans". Dr. Mikovits reported the same thing; that there are anti-retroviral drugs sitting on drug company shelves that they did considerable research on but which never made it to market but which might be able to be employed on fight on XMRV. If thats true it gives the medical community a nice head start on this virus.
  
  Dr. Bell has been able, thus far, to find about 40 of the 60 patients from his original Lyndonville cohort. He'll be testing them for XMRV in Dr. Ruscetti's lab.
• Dr. Bateman Talks - Dr. Bateman also gave a talk recently on XMRV. According to someone who attended one of the things that stuck out was how different her patients were from the patients in the Science study. If you remember the patients in the Science study were disabled, had RNase L and other immune problems and very low VO2 max scores on repeat exercise tests. Dr. Bateman reported that while a significant number of her patients may be tending that way only about 10% of them are currently that poorly off. Dr. Bateman asked Dr. Peterson at the CFSAC meeting if he thought the XMRV findings would apply to 'typical' ME/CFS patients but he didn't to speculate on that. Dr. Mikovits has said, though, that 95% of subsequent tests on ME/CFS have been positive.
• A new Lab in the Mix - We know (or we hear) that labs across the country are furiously trying to develop their own XMRV test. Now our source in Utah has identified one for us. The Hepatitis-Retrovirus lab at ARUP is reportedly 'well into" developing their own tests. (One of their researchers, Dr. Ila Singh has been studying XMRV for several years.) Why do we need more tests? We may very well need not them but the more sophisticated labs that dig into XMRV the better chance that we'll know more and more about this virus.
  
  Thus far we know of three labs that have taken the XMRV 'challenge'; VIP Dx (associated with the WPI), ARUP in Salt Lake City, Utah, and Cooperative Diagnostics in South Carolina. Surely more research laboratories are engaged as well. 

Dec 11th

• Dr. Mikovits Grand Rounds Presentation at the University of Florida College of Medicine on Oct. 20th. In Grand Rounds p presentations researchers or physicians simply talk to and get questions from physicians, researchers and students at a Medical School. In this short article on Dr. Mikovits presentation we find out that those XMRV positive multiple sclerosis, autism and FM patients the WPI announced were actually relatives of their CFS patients. Isn't that an interesting fact in itself: that ME/CFS patients perhaps have a high incidence of MS, autism and FM in their family. Sure sounds like neuro-immune territory (XAND?). Check out the article here.
  
  Dr. Mikovits also reported that all the lymphoma patients at the WPI clinic tested positive for XMRV. (Check out more on the ME/CFS Lymphoma findings here)

Dec 10th


• Podcast on XMRV with Dr. Vincent Racaniello, the Columbia professor who's been bloggin on XMRV. His piece on XMRV is about 30 minutes in the futures of Biotech 50 podcast.
• Dr. Judy Mikovits - the Scientific Director of the WPI (and the one who came up with the idea to search for XMRV in ME/CFS patients - will do a live Q&A on Prohealth on Jan 22nd.
• Article on CFS with XMRV in it - the CFIDS Association just provided a link to a Woman's Day article on CFS. Its another good article. I've known for several years a real change in the media's attitude towards ME/CFS; its hard to find a bad article on it anymore. Of course the XMRV finding has sped up that process greatly.
  
  
• University of Pacific Talk Embargoed - Just days before the exciting CFSAC presentations by Dr. Peterson and Dr. Coffin, Dr. Mikovits - the Science director of the WPI - made what was described as an even more far-reaching 2 1/2 presentation at the University of the Pacific. A camera crew was there to film it. We were told it would be a week or two and...that was the last we heard of it. Apparently the talk has been embargoed by the WPI because it was very far-reaching indeed and they want to get some more data published before the video is released.



• VIP Dx Labs Slow Pace - Several people have noted that its taking quite a while to get their test results back and we may have found out why. One of the people on the Phoenix Rising Forums reported that her doctor checked in and learned that they are simply because as she put it "they're absolutely swamped".
• Phoenix Rising XMRV Forums - have changed; instead of one forum we have three: Research and Replication / Test, Treatment and Transmission and Media, Interviews, Events, etc. Check them out!


Dec 8th

• AZT for XMRV?
  
  A recently released study examined how effective 10 anti-HIV drugs were against XMRV. The bad news was that none of the drugs stopped XMRV activity; the good news was that AZT block XMRV from replicating and from infecting other cells. Thus none of the drugs touched XMRV while it was in the cell but AZT stopped it from spreading and doing its mischief once it emerged from the cell.This was a laboratory study which means the results may or may apply to the more complicated situation in the body.
  
  Follow the discussion on AZT and XMRV on the Phoenix Rising Forums here.

Dec 7th

• The XMRV Testing Polls
  
  We have a variety of polls running on the Phoenix Rising Forums about the results from XMRV testing. They're using Dr. Bell's Disability Scale to see how people with severe, moderate, mild cases of ME/CFS shake out. Even though the test has been available for over a month the results are coming in very slowly. Thus far of 7 people tested using either the VIPDx or the Cooperative Diagnostics Tests two have tested positive. Check the polls out here; they're at the top of the page.
  
  Check out some discussions on the test results and why it's taking so long to get results .
  
  Test results should be flooding in pretty soon as the VIPDx starts whipping out more results and patients get in to see their doctors.
  
  Thanks to the Forum participants we were able to add a few more replication studies to the list below. There appear to be at least seven pretty well confirmed studies ongoing.

Dec 5th

 The XMRV /XAND Pages 

Info





• Information Center
• XMRV Buzz - The Latest News' -
• Resource Center
• Ongoing XMRV Studies
• Discuss It 

Testing, Treatment and Transmission





• Testing
• Treatment
• Transmission

The Science





• Overview
• Hope and Caution
• Proving XMRV - The Next Steps
• Dr. Klimas on XMRV Pt I
• Dr. Klimas on XMRV Pt II
• Dr. Peterson at the CFSAC
• Dr. Coffin at the CFSAC
• Dr. Coffin/Peterson Q & A at the CFSAC
• The Puppet Master
• The XMRV Replication Studies
  
  Just how many XMRV studies are occurring? Here's what I've found so far:
  
  
  • The CDC's HIV division study involving WPI samples, Wichita/Georgia samples and hopefully samples from other CFS groups
  • a large set of studies under the aegis of the Health and Human Services Working Working Group on XMRV in the US (see below)
  • Dr. Nancy Klimas - ME/CFS patients in her ongoing "Good Day: Bad Day" Study
  • Dr. Nancy Klimas - Gulf War Syndrome patients
  • a UK study involving Dr. Kerr and including samples from Dr. Enlander in the US  - Target Date - Summer 2010
  • another UK study from the University College London
  • a Swedish study  - Target Date - Spring/Summer 2010
  • Cornell University in cooperation with the Columbia University Center for Infection and Immunity and the Whittemore-Peterson Institute are embarking on a study assessing XMRV status in relation to functionality
  • the Cooperative Diagnostics Lab in South Carolina
  • A report from the Phoenix Rising Forums stated the Dr. Joliceur at L'Institute de recherche attached to the University of Montreal in Montreal, is doing a study with 50 patients.
  • Dr. Bell skis getting in touch with his original pediatric Lyndonville cohort from the early 1980's. Dr. Ruscetti of the National Cancer Institute will test them in his lab.
  • Dr. Shepard of the MEA reports four 'very good' research groups are 'very keen' to do followup studies and that money is not a problem
  • Dr. Lloyd in Australia hoped to get one together to test his Dubbo patients but its unclear whether he did
  More are undoubtedly ongoing; if you know of more please contact me (phoenixcfs@gmail.com)
• More on the Two German XMRV Studies Inability to Find XMRV
  
  Two German studies have been unable to find XMRV in prostate tissue or CFS patients blood. What might explain their inability to find this virus? Dr. Silverman suggested three things; one, since they used different techniques their findings could be different, the XMRV strain in Germany is slightly different and thus PCR didn't pick it up and XMRV simply isn't as prevalent in Germany as the US.
  
  Since PCR studies 'find' a virus by searching for tiny bit of its genome if that part of its genome is slightly different in Germany than it is in the US a PCR study will not pick it up. Since the virus was genetically quite uniform across the US it doesn't seem likely it would be markedly different elsewhere but it is a possibility. If the third possibility is true then XMRV must be very rare in Germany since the study didn't find any XMRV in almost 600 patients.
Dec 4th
• More From Dr. Vernon on XMRV - in the CAA's latest CFIDSLink - One of Dr. Vernons jobs as the Scientific Director of the CFIDS Association is to network with ME/CFS researchers. In this elink she remarks on how the XMRV discovery rocked their world (as well as ours). She also reminds us of the rather long road ahead to validation and how vital other research remains.
  
  "Many readers may not realize the incredibly competitive and political nature of science. To most of the CFS medical and research community, the XMRV finding published in Science was a surprise announcement. While many investigators were cautiously optimistic and excited about how this could be a game-changing finding, some were ready to “pack up and go home” – mostly because the media blitz read like a “case closed” Sherlock Holmes novel."
  
  "It takes only a brief review of lessons learned from other remarkable discoveries like HIV to understand that detecting a virus is the beginning. If the XMRV finding is replicated in other CFS populations, validated to be the cause of CFS, and the FDA reviews the quality of XMRV diagnostic tests, then we can “check off” objective diagnosis from our to do list! XMRV is a new beginning, not the end."
  
  "Personally, I hope XMRV is validated and found to be the cause of CFS – finally we will have a context for all the important and remarkable ongoing research. And in no way does XMRV reduce the importance of ongoing research on immune dysfunction, other pathogens, post-infection fatigue, dysautonomia, HPA axis dysfunction, oxidative stress and altered neurometabolism, etc. On the contrary, it gives these investigators a strategic advantage and a competitive edge for CFS funding opportunities that will advance treatment and prevention."
• The Health and Human Services (HHS) Working Group for XMRV - The CFIDS Association of America reports that this group will have oversight over the federal effort on XMRV. They will investigate XMRV regarding its presence in the blood supply and CFS. Dr. Suzanne Vernon, the CFIDS Association's Scientific Director will be part of the group along with representatives from the NIH, CDC and FDA. It appears to be a large effort indeed. 
  
  Regarding CFS the group is taking a three stage approach:
  
  
  1. First they will attempt to standardize and validate tests for XMRV. Then they'll test 1,200 healthy donors and 100 patients provided by the Whittemore Peterson Institute.
  
  
  2. Secondly they'll assess the prevalence of XMRV in the general populations, the blood supply and in other groups of people with CFS
  
  
  
  3. Lastly they'll dig into to how XMRV is transmitted , what effects it may have and how it may affect other groups
  
  
  For more on the HHS group click here.
• Preliminary tests suggest XMRV may not be found in German ME/CFS patients. From the Phoenix Rising Forums:
  
  This test was run at the Charite - one of the largest universities in Europe. Le Charitie is a medical research center/school sponsored by the Free University of Berlin and Humboldt University.
  
  "From the Institute for Medical Immunology (Nov 30, 2009): Recently a workgroup from the NIH and WPI described a new retrovirus XMRV as associated with CFS in US patients. Since then the Robert Koch Institute has tested German patients with CFS for XMRV. The provisional results are different than in the US, as the patients tested so far are rarely infected with XMRV. Further tests are underway in cooperation with the US groups. In the meantime we can not recommend XMRV testing (for CFS). In fact the study from the US does not prove that XMRV causes CFS, only that XMRV is present in CFS patients and has been present for a long time." http://immunologie.charite.de/news/news/xmrv-beim-cfs/
  
  Several factors including the type of patients being studied and the type of test used make it difficult to interpret this finding. A German team that failed to replicate XMRV findings in prostate cancer engendered questions whether XMRV is found in Germany.
  
  Check out discussion on this topic on the Phoenix Rising Forums
Dec 3rd
• Dr.  Oz  interviews Dr. Donnica Moore, a physician with a son with ME/CFS, for 12 minutes about XMRV and ME/CFS. The video is not up yet but a short article is.  Better yet here's an overview of the program by Mardy Ross
Dec 2nd
• The Q&A from the Federal Advisory Committee Meeting's (CFSAC) Session on XMRV is available as text.
• Dr. Vernon explains what the CFIDS Association of America is doing on XMRV:

  "Since we learned about XMRV through the press release issued by WPI, NCI and Cleveland Clinic and then the Science paper once it was published, we have been busy gathering additional information on the many research and policy implications this important study brings. There are many investigators interested in replicating these findings who need funding to do this work.
  
  At the CFSAC meeting in October, investigators with NIH existing grants were encouraged to apply for supplemental funding, so we contacted funded CFS investigators to encourage and support supplemental requests. This has involved "matching" lab researchers to clinicians who can provide appropriate patient and control samples for testing. We are currently raising funds through our "SolveCFS Campaign" in hopes of issuing another request for proposals (RFP) aimed at early detection, objective diagnosis and treatment of CFS; XMRV proposals would certainly be responsive to such an RFP. 
  
  We are also seeking up to date information from the various federal agencies now involved in the XMRV research and response.  Interestingly, the detection of XMRV in 3.7% of healthy controls, as reported in the Science paper, raised potential concerns about the safety of the general blood supply.  As also discussed at the October CFSAC meeting, the significance of XMRV in the blood supply will be determined by investigators who are expert in dealing with blood supply safety issues and have experience with other infectious agents that could compromise the blood supply.
  
  We are working closely with many different institutions and agencies with each new development so that we understand what types of optimized XMRV assays will be most effective for use in larger studies that will advance collective understanding of the role of XMRV in CFS. Although in many ways  the past 2 months have been hectic the CFIDS Association has been doing what we have always done and do best – advocating for and supporting research aimed at the early detection, objective diagnosis and effective treatment of CFS through expanded public, private and commercial investment."

  Dr. Vernon was Phoenix Rising's Researcher of the Year. Check out more on Dr. Vernon here. .

Nov 29th

• Dr. Vernon talks about how the XRMV finding may affect other research - in particular cortisol.
  
  Question: XMRV is a really exciting, really hot finding. A lot of non XMRV research findingsnbsp; have been developed over the years; there’s the low blood volume, the HPA axis abnormalities, the  metabolic related exercise problems, the orthostatic intolerance, the gastrointestinal enterovirus findings, etc. There are alot of research findings that can’t at least at this point be directly linked to XMRV. Lets say XMRV is the ‘Game Changer’ in ME/CFS; will research focused specifically on those areas still be relevant?
  

  "Absolutely relevant!  I hope that XMRV is replicated as it provides a clear biologic basis for CFS and a context for the ongoing pathophysiology CFS research. Once this is done, we will potentially have a context for low blood volume, the HPA axis abnormalities, XMRV, etc.  It is worth noting that even though we can detect HIV and have antiretroviral therapy, people who are managing their HIV infection still have a variety of health issues to deal with including serious endocrine and metabolic problems to name a few."

• The HPA axis is our body’s “flight or fight” 24/7 system – in other words, it gets activated when the body needs to respond.  This can be in response to infection, physical trauma, stress, etc.  The HPA axis is also a very dynamic system that must respond when needed and stand down when not needed.  Cortisol is one of the major chemicals that mediate the HPA axis response system.  When the HPA axis system is alerted, cortisol is produced by the adrenal glands and pumped out into the circulation.  There it signals to immune cells to produce cytokines to help fend off the infection or heal the wound.
  
   "Immune cells do this because the cortisol enters the cells, binds to the cortisol receptor in the cell and this complex moves into the nucleus where it regulates cell transcription.  When it is time for the HPA axis to stand down, cortisol travels to the brain and signals to the hypothalamus to return the HPA axis to standby.  There are several viruses that can persist and remain latent in immune cells.  It is possible that these viruses alter the function of the cell where they reside."
  
  Dr. Vernon was Phoenix Rising's Researcher of the Year. Check out more on Dr. Vernon here. .

Nov 28th

• Dr. Coffin's testimony from the CFSAC is now available in text on Phoenix Rising - thanks again to Garcia

Nov 27th

• CFIDS Association announces that an interagency task force on XMRV has been set up. "In recent weeks, the U.S. Department of Health and Human Services has formed an interagency task force that is meeting regularly to appropriately replicate the CFS studies, address validation studies, development of appropriate screening and diagnostic tests, and to address the safety of the blood supply. There has not yet been a formal statement from the Department about this interagency effort..." WildDaisy on the Phoenix Rising forums e-mails Wanda Jones who fills in the blanks and its  big news indeed; the federal government is mounting a large effort on XMRV.
  
  "FDA, NIH, CDC--the agencies responsible for blood safety, as well as several non-Federal groups (are members). The team is drawn from the retrovirus expertise of the agencies. They are developing several "panels" of thousands of samples drawn from blood donors, from CFS patients, people with other diagnoses, etc. They are taking fresh as well as repository whole blood samples, not serum. They have standardized reagents, working with Judy Mikovits. The work is just beginning"
• Dr. Peterson's testimony from the CFSAC meeting is now available in text  on Phoenix Rising thanks to Garcia!

Nov 26th

 

• Swedish XMRV Replication Study Underway in Sweden: Completion Date spring/summer 2010

Nov 25th

• Dr. Timothy Luckett proposes that Raltegravir might be the best candidate for XMRV treatment in his blog. The upside of Isentris is that the virus is probably not going to develop immunity to it and that its fairly safe. The downside is the cost ($1100/month) which may inhibit some insurers for paying for it. For more on Isentris.
• Whittemore Peterson Institute reports on its Facebook page that XMRV is not Dr. DeFreitas virus from the early 1990's
• Dr. Klimas Answers Questions for the New York Times:
  
  
  • I really want to know more about what you think of the specific findings of Dr. DeFreitas. Do you think there are two retroviruses associated with Cfids? I know there needs to be more study, but do you have an educated guess as to how they interact and if they are causative or just epiphenomena?

    For example, if this were solely hypocondriasis or conversion disorder, I would want to know so I could start therapy on it.

    Dr. Klimas responds:

    Elaine DeFreitas’s work and that of Dr. Michael Holmes of New Zealand both involved scanning electron micrographs of viruses. Their findings look a great deal like those that were published in the recent Science article by Dr. Lombardi and colleagues, whichMs. Grady wrote about in The Times,) that found a possible link between chronic fatigue syndrome and the XMRV retrovirus. Could they be looking at the same virus? I don’t really know, because I am not a laboratory virologist. But it makes good sense to me. (the WPI recently reported the virus is not Dr. DeFreitas viru

    I remember in the early 1990s a member of our laboratory, Dr. Roberto Patarca, found evidence of production of an enzyme called reverse transcriptase in our cell cultures, more evidence of an active retroviral infection. So the key thing now is for another reputable lab to find the same thing in chronic fatigue syndrome. Then we will see what happens next.
    
  • I find the new research hard to believe, especially the follow-up research that shows 98 percent of patients who receive a clinical diagnosis of C.F.S. tested positive for the retrovirus, compared with only 3 percent of controls. Why hard to believe? It is almost impossible to be 98 percent accurate with most clinical diagnoses, especially those without specific tests, like C.F.S. Please comment.

    Dr. Klimas responds:

    Well, it is hard to comment on unpublished data — the number of patients who were shown to be positive for C.F.S. by antibody testing has not been established.

    There are likely to be wide differences when these prevalence studies come out — as you point out, where the investigator gets the blood will matter. Investigators will need to be very clear how they defined the illness, where they got the samples, the demographics of the population, and any defining subgroup information. In my clinical immunology clinic, for instance, there may be more patients with a post-viral or acute onset type of C.F.S. than other medical practices. A rheumatology clinic, for example, may have a stronger fibromyalgia overlay to the population.

    In the population-based Georgia study conducted by the Centers for Disease Control and Prevention, investigators used a broader case definition and identified a population with C.F.S. that was fivefold larger than previous prevalence studies. That study may have included people with other disorders that cause fatigue, and I would expect to see up to a fivefold difference when compared with a more tightly defined group. There may also be regional differences in the prevalence of the XMRV virus that was recently linked to C.F.S. A European study that failed to find the virus in prostate cancer samples suggested that there might be differences in the background population prevalence rate of the virus.

Nov 24th

•  75 XMRV researchers meet  at the Cleveland Clinic for a 10 hour meeting on XMRV, the blood supply, CFS, etc. on November 11th
• Whittemore-Peterson Institute posts note on how to contact your representatives to advocate for more research into XMRV