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XMRV CFS UK study #II

Discussion in 'XMRV Research and Replication Studies' started by Orla, Feb 15, 2010.

  1. Quilp

    Quilp Senior Member

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    lol@Robin. Very well put Robin, though it does seem a little incongruent amongst the intricate forensic analysis taking place on this thread ! Wow you guys are amazing thank you so much. I recognise that you are poorly too, and to put so much effort into your analysis is fantastic. Thank you.

    I think the good news is that some of the greatest minds in the world are working on this puzzle. Who would have thought this a few years ago ? Who would have thought that we'd get a mention in Science ? I cannot countenance a situation whereby all those involved walk away from this shrugging their shoulders. At the very least we are going to be left with a paradigm shift away from the psychiatric strangle hold. For decades the psychiatrists have had us pinned up against the wall. Well guess what, we have just kicked them in the b*****ks and they really don't like it do they.....

    I am also concerned that this might slow the number of patients sending their samples to VIP DX. Lets not forget they have sampled over 500 patients and achieved a 50% 'success' rate. By default this is the largest 'study' group yet carried out, and using 'blind' cohorts. Will this have a spiralling effect ? No samples to test, no revenues to generate, no scientists to pay, nobody to do the tests.

    Down, but not out....
  2. Marco

    Marco Old blackguard

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    Your right that on shouldn't necessarily jump to conspiracy theories and I'm not suggesting for one minute that this research wasn't well intentioned. But.

    Having faith in the scientific process assumes that it is a level playing field. Hooper's Magical Medicine paper (see thread) strongly suggests that the playing field is far from level. Therefore the science is necessary but possibly not sufficient.

    I'm afraid I have to return to the statement made by the minister responsible for the Medical Research Council in response to a parliamentary Question on MRC funding of research into psysiological causes of ME. The written answer dated just last December made no mention of a study of XMRV in ME. Yet this study appears in early February apparently funded by the MRC. As is often stated the MRC is a public body independent of government. However, regardless of how independent, they are still a public body and bound by strict standards regarding the use of public money. Any funding of research must follow strict procedures and be open and transparent. Given the MRC's previous apparent reluctance to fund physiological research I find this rapid turnaround surprising. If the methodology used here was 'quick and dirty' from the perspective of using banked blood samples it still doesn't leave much time to go through the funding process and even a 'quick and dirty' study needs to go through the proper process if public funds are involved. It also doesn't seem a consistent approach compared to the MRC's stated aim of research excellence. There is probably a simple explanation for the genesis of this study but we haven't seen it yet.

    Getting back to the science this is way outside my field but can't help wondering :

    Am I correct that the original WPI cohort that yielded a 67% positive was considered as a 'pure organic ME' cohort because it resulted from an epidemic cluster? Perhaps epidemic outbreaks are atypical.

    Also, as has been discussed on another thread, is it possible that XMRV is present in say 4% of the general population but isn't 'activated' until it comes into contact with another virus, vaccine or virus/other stressor. Rather than the RNA retrovirus activating in the host organism, it invades the other virus and lateral gene transfer creates XMRV hybrids. In these circumstances you might expect geographical variations in the hybrids.

    Could WPI have identified a localised hybrid (likely if an epidemic cluster was the original cohort) and from this identified the retrovirus markers, but assuming they were dealing with one ubiquitous virus, sent samples of the full hybrid genome to others?

    If I need to go and lie down again, please let me know.
  3. Cort

    Cort Phoenix Rising Founder

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    Unfortunately Dr. Mikovits made it pretty clear that the samples in the Science study were from all over the US and from the UK, Germany, Italy and Australia - they got a wide representation of patients from around the world. It is possible, I suppose, that the negatives from PCR were from outside the US but that's just speculation and surely we would have heard of that by now. y Dr. Mikovits may have cracked the code on those samples to see if the international patients were showing up negative by PCR but positive by another means. Given the wide spread of the patients the geographical variation theory doesn't seem to be very strong. It really seems to come down to the testing process (?)

    Good point Quilip. One would think another negative study would have a dampening effect on interest. Still all those studies are underway - hopefully this is not enough reason to shut them down - and that's what we really need - is more rigorous study. Certainly it won't have any impact on the big studies; the DHHS and CDC studies.
  4. Orla

    Orla Senior Member

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    More detailed MEA statement

    MAY BE REPOSTED

    This is a more detailed ME Association summary and position statement. It replaces the one issued shortly after publication of the paper in Retrovirology by Groom et al on 15 February

    ABSENCE OF XENOTROPIC MURINE LEUKAEMIA VIRUS-RELATED VIRUS (XMRV) IN UK PATIENTS WITH CHRONIC FATIGUE SYNDROME

    RETROVIROLOGY: 2010, 7, 10 (published 15 February 2010)

    An abstract of the research paper can be accessed here: http://www.retrovirology.com/content/7/1/10/abstract

    The full paper can be accessed via a provisional PDF on the Retrovirology journal site.

    Background

    A second UK research group has reported that they have been unable to find any laboratory evidence of XMRV (xenotropic murine leukaemia virus-related virus) infection in people with ME/CFS.

    This follows another UK study involving Kings College Hospital, London (for patient selection) and Imperial College, London (for laboratory investigation) which, again, found no evidence of XMRV infection in 186 Fukuda defined CFS patients. An MEA statement and link to this KCH/IC paper can be found in the January news archive on the MEA website.

    Researchers involved

    The latest UK research, which has been published in the on-line edition of Retrovirology, was carried out by a collaborative of very reputable virologists and retrovirologists. The group includes two researchers - Professor John Gow and Dr Jonathan Kerr - who are already involved in biomedical research into various aspects of ME/CFS and Dr Jonathan Stoye, from the National Institute for Medical Research. Dr Stoye co-authored the editorial in Science that accompanied the paper from the American (WPI et al) group which found evidence of XMRV infection in 68/101 ME/CFS patients and first raised the possibility of a link between XMRV and ME/CFS back in October 2009. The Science paper, and the accompanying editorial by Coffin and Stoye, can be accessed via the full XMRV summary on the MEA website.

    ME/CFS patient selection

    The UK research involved the use of stored blood samples taken from two cohorts involving 170 people with Fukuda research defined CFS and three cohorts containing 395 controls (mainly healthy blood donors).

    The patient samples came from people with ME/CFS who had been seen in medical clinics in various locations around the UK (ie Birmingham, Bristol, Dorset, Epsom, Glasgow, London, Norfolk), including some supplied by neurologists Professor Peter Behan and Dr Abhijit Chaudhuri. Unlike the American study, which only involved people with ME/CFS who met both Fukuda CFS research criteria and Canadian clinical criteria for CFS, the UK patients only met Fukuda CFS research criteria. The reasons why most (possibly all) research groups who are quickly attempting to replicate the US/WPI et al findings are not currently using Canadian clinical criteria are explained in more detail in the MEA summary on XMRV.

    Laboratory methods used to detect evidence of XMRV infection

    The UK researchers looked for evidence of XMRV infection using two laboratory techniques

    Firstly, quantitative PCR (polymerase chain reaction) to check for the presence of viral nucleic acids (ie DNA). The PCR employed is capable of detecting as few as 16 copies of proviral DNA - viral DNA (genetic material) that has been integrated into human chromosomal DNA. The authors state that this technique is likely to be as sensitive, if not more so, than the assays used in the US/WPI et al study. No XMRV sequences were detected in 142 CFS samples and in 157 controls.

    Secondly, a viral neutralisation assay to try and detect an anti-XMRV immune response. In simple terms this means looking for evidence of antibodies that could prevent infection of cells with the XMRV infection. None of the 142 CFS samples contained antibodies that could block XMRV infection of the cells. Although 22/157 control samples were identified that contained neutralising antibody, he authors concluded that the strong positive neutralising activity demonstrated in some of the blood donor controls was not specific to XMRV, and in all likeliness this was not elicited by this virus. One sample of CFS serum from a separate cohort of 28 was found to contain neutralizing activity

    Study conclusions

    The authors emphatically report that they have not identified XMRV DNA (ie viral genetic material) in any samples using PCR (0/299). Some serum samples showed XMRV neutralising activity (26/565) but only one of these positive sera came from a CFS patient.

    Those involved in this study concluded that:

    No association between XMRV infection and CFS was observed in the samples tested, either by PCR or serological methodologies. The non-specific neutralisation observed in multiple serum samples suggests that it is unlikely that these responses were elicited by XMRV and highlights the danger of over-estimating XMRV frequency based on serological assays. In spite of this, we believe that the detection of neutralising activity that did not inhibit VSV-G pseudotyped MLV in at least four human samples indicates that XMRV infection may occur in the general population, although with currently uncertain outcomes.

    Comments from the MEA

    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.

    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/index.php?option=com_content&view=article&id=30&Itemid=205 - will continue to consider applications for research funding for any aspect of XMRV research.

    XMRV summary

    The most recent MEA summary on XMRV can be accessed using the Quick Links section on the MEA website: http://www.meassociation.org.uk

    Dr Charles Shepherd
    Hon Medical Adviser, MEA
    16 February 2010

    ENDS
  5. Katie

    Katie Guest



    Can you tell us more about this, for example who these 'people' are? Third hand rumours give me the heebie-jeebies.
  6. Bob

    Bob

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    Yep, the twists in this story are intriguing...
    But the WPI really can't be wrong about XMRV... they have so much evidence that it's a new(ish) human retro-virus... they even have microscope photographs of the little buggers (I think - don't they?)
    If the WPI have developed an even more sensitive test, then this is even more good news for us... they striding forwards with this research and leaving all of the other labs behind.
    All the other research teams, who are testing negative all the time, either need to replicate the WPI research or shut up about it... what's the point in telling the world that they aren't very competent researchers?
  7. Bob

    Bob

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    Thanks Quilp... I think we all need to hang onto this thought.
  8. Katie

    Katie Guest

    Charles Shepherd really can bea bit of a wet lettuce sometimes.


    Comments from the MEA

    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. Why must? A significant proportion? This is complete conjecture, the study says Fukuda not Canadian Consensus. No one in Shepherds position should be making claims unless he knows that a significant proportion met both criteria. This grated on me. I've had ME for thirteen years, I will not go to the Norfolk clinic to be told how my thinking is holding back and to do a little more each day, no way, I'm doing fine on my own listening to my body. Maybe I should go. 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.

    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. This is THE most important point, he should be focusing on this aspect. I'd be quite happy for funding to be directed to this cause alone and keep ME out of it for a study, just the retrovirus. 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. Yet says earlier that positives and nagatives from the UK can be supplied to the UK studies to help out. There's more to gain than personal illness management and I've got the Canadian Consensus to tell me I have ME. Oh, and thirteen years experience.

    The MEA Ramsay Research Fund - http://www.meassociation.org.uk/index.php?option=com_content&view=article&id=30&Itemid=205 - will continue to consider applications for research funding for any aspect of XMRV research.

    XMRV summary

    The most recent MEA summary on XMRV can be accessed using the Quick Links section on the MEA website: http://www.meassociation.org.uk

    Dr Charles Shepherd
    Hon Medical Adviser, MEA
    16 February 2010

    ENDS[/QUOTE]
  9. Marco

    Marco Old blackguard

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    Thanks for the correction Cort. Could someone please remind me how this international cohort came to be diagnosed according to the Canadian definition?
  10. Hysterical Woman

    Hysterical Woman Senior Member

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    Hi Guys,

    I am confused about the definition of "replication" study means in a strict scientific sense. I searched around and couldn't come up with anything definitive. FWIW I did find this on Wiki on reproducibility:

    http://en.wikipedia.org/wiki/Reproducibility

    Anybody got a strict defintion?

    Thanks,

    Hysterical
  11. George

    George Guest

    The patients in the original study were taken from Dr. Peterson practice. He has people from all over the world go to him for initial consultations and lab work. Then he send info to the persons treating physician. A) he's a really good diagnostician and B) he tends to get only the really sick people who are desperate and c) he's a believer in the Canadian Criteria.
  12. anne

    anne Guest

    George, I thought they were from about five different doctors, including Klimas?
  13. Mithriel

    Mithriel Senior Member

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    You are right Katie, I don't see any way that you could confidently say that a significant proportion must meet the Canadian Guidelines.

    They don't say what sort of blood was used. Does everyone who attends a clinic get their blood stored? If so, how did they choose which ones to test? Considering how snide so many commentators were about the WPI not giving enough details of their samples this seems a bit much.

    I am sure that people who have just developed ME/CFS may well be attending the clinics but I wonder if they will have as much XMRV in their cells. If PCR could be done for HIV all those policemen and medical workers who get needle stick injuries would not be left waiting for six months to know if they have HIV.

    In the UK, the clinics are mental health, no matter how they dress it up, and those who strongly believe they have a virus are loathe to attend. Even the ones who are very sick may not have XMRV, lots of things are misdiagnosed as CFS. The emphasis is on fatigue and many things cause that. No one has claimed that fatigue is caused by XMRV and things like chemotherapy can cause a long lasting fatigue without a retorivirus having to be involved.

    I don't think this study deliberately used bad samples but we will need a tighter group of patients to be studied in future.

    Mithriel
  14. Navid

    Navid Senior Member

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    yes....i'll be in the trial!!!!!!!!!!

    how are you sue?

    take care, lisa:victory:
  15. George

    George Guest

    You're right, different doctors, it doesn't say who the doctors were though.

  16. Katie

    Katie Guest

    I meant like a limp wet lettuce, but I'll edit mine if you edit the quote!
  17. oerganix

    oerganix Senior Member

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    XMRV Discussion on Faculty of 1000

    For some encouraging statements from docs and researchers re:the organic basis for ME/CFS see this blog:
    http://cfs-facts.blogspot.com/2010/02/xmrv-discussion-on-faculty-of-1000.html

    It's very heartening to know that there are many who do realize this is organic in nature and aren't bamboozled and dazzled by all the psuedo-science that has been put out over the decades.
  18. michal

    michal

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  19. Bob

    Bob

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    I disagree with Dr Charles Shepherd...
    All that these UK studies show us is that they didn't replicate the WPI research, and that the researchers have failed to detect an extremely-hard-to-detect virus.
    Now the researchers need to replicate the WPI research, use some proper ME patients to test (I'd volunteer), stop messing about with these silly games, and do some proper research!
  20. Bob

    Bob

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