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ME Association (UK) Summary & Statement on Lo/Alter et al Paper

Discussion in 'Media, Interviews, Blogs, Talks, Events about XMRV' started by pictureofhealth, Aug 25, 2010.

  1. pictureofhealth

    pictureofhealth XMRV - L'Agent du Jour

    Here is the full statement from the UK's patient charity the ME Association on the Lo et al paper.

    They are unable to post on their website at the moment, so there is no direct link for the full document anywhere else but have agreed that we can repost here in full.




    Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors

    Authors: Shyh-Ching Lo (US Food and Drug Administration) et al.

    Published in the Proceedings of the National Academy of Sciences (PNAS) on August 23rd 2010.

    Pdf available on-line: html

    Accompanying commentary by Valerie Courgnaud et al: html


    Murine leukaemia viruses (MLV) are retroviruses known to cause cancer in certain mice. In 2006, investigators found that a type of MLV, called xenotropic murine leukaemia virus-related virus (XMRV), could potentially infect humans after finding it in tissue samples from men with prostate cancer. XMRV is one of a number of MLVs that appear to be transmitted to humans.

    In October 2009, Lombardi et al published the results of study in Science which contained evidence that XMRV was present in a high percentage (67%) of people with ME/CFS and in a small percentage of healthy controls.

    Since then there has been a great deal of interest from researchers in a number of countries where ME/CFS is recognised. A number of research groups have attempted (or are still attempting) to repeat these positive XMRV findings.

    Confirming or refuting new findings is a vital part of the scientific evaluation process and involves other independent research groups trying to either replicate or validate the results.

    In relation to XMRV, a true replication study should involve exactly the same laboratory methods and same type of patients that were used in the original Science study. A validation study gives scientists a degree of flexibility. In particular, it provides the opportunity for other research groups to try and repeat the findings using what they feel are the most sensitive and accurate laboratory methods they have access to for testing for XMRV.

    In the case of XMRV almost all of the first wave of research has involved validation studies. Firstly, because there is no international agreement about the most accurate and sensitive way of detecting XMRV in blood samples. Secondly, because these research groups all wanted to move quickly, and the easiest way to do so was to use stored blood samples from people who had been diagnosed with CFS in the past according to Fukuda research criteria. Stored blood samples from people who met both Fukuda and Canadian criteria (which were used in the original study) are not readily available.

    Results from four emphatically negative validation studies of varying quality - three carried out in Europe and one carried out by the CDC in America - have now been published in scientific journals. Results from a further (so far unpublished) study, carried out by Professor Brigette Huber, were presented at the Invest in ME conference in May 2010 (report available on MEA website and in the August 2010 of ME Essential).

    None of these five research groups - which in the case of the UK included Professor John Gow, Dr Kate Bishop, Dr Jonathan Kerr and Dr Jonathan Stoye and used patient samples supplied by physicians and neurologists including Dr Abhijit Chaudhuri and Professor Peter Behan - have been able to find evidence of XMRV in blood samples from ME/CFS patients, or in the healthy controls.

    Although some very valid criticisms have been made about all of the XMRV negative studies, in particular the most recently reported one from America, a number of distinguished virologists who work with retroviruses and XMRV have been involved - so these XMRV negative results have to be taken seriously as well.

    THE LO et al STUDY

    On 23 August 2010 the results from the first follow up study to firmly support a link between a retroviral infection and ME/CFS were published.

    This study is clearly an important contribution to the XMRV debate in that it fully supports a link between ME/CFS and retroviral infection. In this respect it also supports the findings in the Lombardi paper.

    However, it is not a true replication study, and in the words of the authors they have not attempted to fully replicate the Lombardi et al findings.

    Lo et al have used different laboratory methods and different patient criteria and their findings relate to what are called MLV-related viruses.

    The research group have found segments of genetic material (not whole virus) from what they term a genetically diverse group of MLV-related viruses. These sequences are more closely related to those of polytropic mouse endogenous (=arising within or derived from the body) retroviruses than to those of XMRVs - hence the use of the term MLV (murine = mouse leukaemia virus) in the title. But they all belong to a closely related family of retroviruses.


    In contrast to the Lombardi et al study, which involved patients who met both Fukuda research criteria and Canadian Clinical Criteria for CFS, this research used stored blood samples from ME/CFS patients who had been diagnosed using either the 1988 Holmes research criteria or the 1994 Fukuda research criteria. The patients were diagnosed with CFS from the mid 1990s onwards and most of the frozen blood samples were supplied by Professor Tony Komaroff at Harvard Medical School, Boston. Professor Tony Komaroff is a well respected physician with a longstanding interest in ME/CFS. In addition, 12 patient samples came from other US physicians whose diagnostic criteria for ME/CFS is not stated.

    The numbers involved were surprisingly small for a study of this nature: 37 patients with CFS and 44 healthy controls.

    The healthy control samples came from Washington DC blood donors recruited between 2003 and 2006.

    So these results apply to a rather broader group of ME/CFS patients than was used in the Lombardi et al study and the patient sample is probably very similar to at least one of the other validation studies that produced negative findings in relation to XMRV. As with some of the other validation studies, it is highly likely that a significant number of people who also meet Canadian Clinical Criteria will have been included in this study.


    MLV-like virus gag gene sequences (in simple terms segments of viral genetic material) were found in 32 out of 37 (86.5%) of the ME/CFS patients compared to only 3 out of 44 (6.8%) of the (blood donor) healthy controls.

    Follow-up samples were collected from 8 of the CFS patients in 2010, and 7 of these again tested positive for MLV-like gene sequences.

    As already pointed out, the evidence in this paper relates to a genetically diverse group of MLV- related viruses with gene sequences that are more closely related to those of polytropic mouse endogenous retroviruses (mERVs) than to those of XMRV. XMRV is a genetic variant of MLV-like viruses - so this is a subtle but relevant distinction.

    The authors point out that they have taken exhaustive steps to try and ensure that they have not produced false positive results as a result of mouse DNA contamination, or any of the other potential laboratory problems that come when working with retroviral infections.


    The authors point out (p5) that the finding of XMRV or MLV genetic sequences in people with ME/CFS, or any other disease, does not constitute definite proof of viral infection.

    They then go on to make it clear that further research will be required before any definite conclusion can be drawn as to whether MLV-related viruses play a role in the causation of ME/CFS. This is a process that is going to take time and further research.

    They also state (p6), as has been pointed out in previous MEA summaries on XMRV, that a high frequency of MLV-related viruses (or XMRV) in ME/CFS patients could reflect an increased susceptibility to viral infections due to the underlying immune dysfunction found in ME/CFS rather than a primary disease causing role in the pathogenesis of ME/CFS. In other words the retrovirus could just be there as a 'harmless passenger'.


    The MEA continues to believe that there is no point in spending very large sums of money on arranging blood tests, which may not have been properly validated, for XMRV (or MCVs) outside the UK. Having a positive result is not, in our present state of knowledge, a diagnostic marker for ME/CFS. Equally, having a negative result does not mean that you do not have ME/CFS. Having a positive result will not affect ME/CFS management at present and if this information is inserted into medical records it could in due course cause problems with other health matters such as applications for insurance policies or travel abroad.

    The way in which these viruses might be transmitted from person to person also remains uncertain and sexual transmission is one possibility - as in the case of HIV. However, if this is a disease causing virus like HIV, sexual transmission appears very unlikely given the fact that ME/CFS appears to be very rare in sexual partners of people with ME/CFS, even after long periods of time.


    The MEA continues to believe that the current uncertainty over transmission of these viruses/viral segments means that people with a current or past history of ME/CFS should not be donating blood and we have recently written to the acting Chief Medical Officer at the Department of Health to seek clarification on what appears to be a recent decision to extend the UK ban to people who have recovered from ME/CFS. Copy of this correspondence:

    We find it surprising that the American authorities responsible for blood safety have not followed the UK lead here.


    The authors of this paper make no comment or recommendations regarding the use of antiviral drugs. However, others (including the authors of the accompanying commentary) are now suggesting that it is time to assess the use of antiretroviral therapy (ART) in ME/CFS in some clinical trials. It is well accepted that one way of examining the possible cause of a disease is to assess the response to specific forms of treatment.

    The MEA has already pointed out on several occasions that this type of clinical trial would have to proceed with great care given the fact that ARTs can have serious side-effects. In the case of AZT, this drug can cause mitochondrial damage - which is obviously very relevant in ME/CFS. But there are other ARTs becoming available that appear to be active against XMRV and may be much safer to use (eg reverse-transcriptase inhibitors such as tenofovir and emtracitabine).

    We have also pointed out that ARTs appear to have very limited effect in reducing fatigue in HIV/AIDS, and that this may be due to the immune system activation that is occurring in this situation rather than any direct effect on reducing the viral load of the HIV infection. So drugs that dampen down immune activity (eg a tumour necrosis factor inhibitor such as etanercept) may be a more appropriate route to follow. More information at:

    In the UK doctors are very unlikely to be willing to prescribe any type of antiviral treatment on an individual (ie non research) basis. This is because the 2007 NICE guideline on ME/CFS specifically recommends that antiviral drugs should not be used to treat ME/CFS. And if anything goes wrong through the use of a potentially toxic antiviral drug, that is in effect banned by NICE, and has not been assessed in a proper clinical trial, the doctor responsible could face legal action even though the patient accepted the risk.


    Investigators at FDA, NIH, CDC and other scientific institutions are in the process of conducting studies to verify the capabilities of the tests used by the different laboratories for the detection of XMRV or MLV-related viruses in blood. These studies are intended to develop and standardise a highly sensitive and specific XMRV test to better study its association with disease, as well as the possibility that XMRV can be transmitted to blood or tissue recipients.

    The UK Medical Research Council's Expert Group on ME/CFS research (of which CS is a member) has identified all aspects of viral infection in ME/CFS (including carefully targeted use of antiviral agents) as a priority item for further UK research and we expect that this recommendation will now be translated into action.

    The MEA is again making it clear to UK research groups with expertise in retrovirology, and access to reliable patient samples, that we would very much welcome good quality research applications relating to any aspect of XMRV or MLVs. The MEA is also willing to consider co-funding research applications in this area.

    We are in contact with most of the key UK researchers working on XMRV and we are also assisting with a small UK study that is intending to retest people who already have a positive XMRV result as a result of having this test done in America.

    We also need to find out how common these new retroviruses are in people with other chronic disabling conditions, especially those that involve immune system dysfunction.


    In America, the paper has been quite widely reported with most of the coverage being supportive. In the UK there has been very little interest in the press release - apart from the Daily Mail (which carried an on-line story) and the New Scientist >> which includes quotes from Professor Myra McClure, one of the UK virologists involved in a negative validation study.

    Lack of coverage in the UK is partly because selected health journalists, who might have reported the story, like to have access to a new research paper well before the information enters the public domain - so they have a day or two to chase around and obtain informed comment on the story. Health reporters have finished writing their copy for the next days paper well before 8pm in the evening - so unless there is a real breakthrough news item they are not at their desks in the evening. The US press conference at 8pm UK time did not fit in with their working arrangements for printing something on Tuesday and the findings would be 'old news' by Wednesday. In addition, they also had a good headline health scare story for Tuesday morning relating to people being refused an anti-cancer drug due to a NICE ruling.

    Unfortunately, there are health correspondents that I speak to on the more influential papers and journals who are now very cautious about covering ME/CFS stories.


    In very simple terms the clinical and scientific community regards published papers rather like goals (of varying quality) in a football match. So the current score is XMRV and MLV positive 2 (with a spectacular first goal!): XMRV negative 4 (of varying quality) with plenty of time left before the final score.

    The comments so far that I have read, or been given, by experts in this area of virology indicate that everything has been done correctly in this study and that this is a sound piece of laboratory research. However, with differing results from differing well respected retroviral laboratories, the clinical and scientific community is likely remain uncertain or sceptical about the link between retroviral infection and ME/CFS.

    Another analogy is fitting pieces into a jigsaw puzzle with a lot of blue sky. We now have six pieces (ie published papers of varying quality) in place and some strong opinions on either side. But a lot of pieces have still to be fitted into the picture.

    Overall, there is no sign of any real scientific consensus emerging as to whether XMRV and/or MLVs are playing a significant role in ME/CFS and many key questions regarding prevalence, transmission and pathogenesis remain unanswered. Things may become a bit clearer as a result on the international meeting on XMRV in September, which will include a session on ME/CFS. Proposals for further research may also emerge after this meeting.

    This uncertainty and scientific disagreement seems likely to continue until well into 2011 and the current findings are unlikely to have any significant influence on the forthcoming review of the NICE guideline or the increasingly difficult position faced by people with ME/CFS in relation to sickness and disability benefits. [Our most recent correspondence on 24 August from NICE indicates that they have still to decide on the date at which the review will take place, whether it will be a full review - which could take up to a year, or whether they might delay the review to await the results of further research from clinical trials.

    More top quality research is clearly needed here in the UK and the MEA is very willing to consider funding it.


    FDA Question and Answer on the paper:

    Answers to the final three questions, which are of importance to US readers:

    9. Does FDA agree with the AABB recommendation to discourage donation by people with history of CFS?

    FDA does not object to the AABB recommendation. The AABB recommendation is consistent with a long-standing position of the Chronic Fatigue and Immune Dysfunction Syndrome (CFIDS) Association of America that individuals with CFS voluntarily should not donate blood.

    10. How are the differences between the CDC and FDA study results being evaluated?

    Differences in the results could reflect differences in the patient populations that provided the samples. Alternatively, undefined differences in the method of sample preparation could be contributing to the discordant test results. All of the scientists involved are working collaboratively to design experiments to quickly answer this scientifically puzzling question. An independent investigator at the National Heart, Lung, and Blood Institute (NHLBI) set up a test set of 36 samples, including known positives and presumed negatives. Both the FDA/NIH and CDC labs participated in this test, and the results showed that both labs were able to detect XMRV present at low levels in blinded samples. Additionally, the CDC laboratory provided 82 samples from their published negative study to FDA, who tested the samples blindly. Initial analysis shows that the FDA test results are generally consistent with CDC, with no XMRV-positive results in the CFS samples CDC provided (34 samples were tested, 31 were negative, 3 were indeterminate).

    11. What do these findings mean to CFS patients and clinicians who treat them?

    Although this study found MLV-like viral gene sequences in a high percentage of CFS patients, this does not prove that these retroviruses are the cause of CFS or of any other disease. Moreover, other studies have not found evidence of such retroviruses in patients with CFS. Further studies are necessary to determine if XMRV or other MLV-like viruses are reproducibly associated with CFS, and if so whether the virus is a causative agent or a harmless co-traveler. The different findings from various studies reinforce the need for more research--including careful analysis of other cohorts of CFS patients from different geographic regions, studies of larger populations of healthy people, and testing of transmissibility of the agents through blood transfusions in animal models. FDA, NIH, and CDC have and will continue to collaborate with other agencies and groups involved in this research.

    Summary prepared by Dr Charles Shepherd
    Hon Medical Adviser, MEA

    MEA website:

    NB: There will be a delay in placing this item on the MEA website because our webmaster is away on holiday for the next few days.

    25 August 2010

  2. Sasha

    Sasha Fine, thank you

    Thanks for posting this, pictureofhealth - a lot to think about there. It was good of Dr Shepherd to press on and write such a detailed piece and allow reposting even when the MEA website itself can't be edited for now.
  3. thegodofpleasure

    thegodofpleasure Player in a Greek Tragedy

    Matlock, Derbyshire, Uk
    Dr Shepherd remains firmly wedded to the past.

    IMO Dr. Shepherd seems to remain firmly wedded to the past and needs to divorce himself from it.

    I'm not at all convinced that he is prepared to accept the idea of retroviruses potentially being causal. His negativity in that respect is evident in the tone and structure of the piece that he has penned. i.e. heavy emphasis on the negative studies and affording them equal weight of importance. Admittedly, it gets better later on, but by then readers' minds have already been influenced.
    With regards to how this plays with the media, I'm affraid that the results speak for themselves.

    The MEA knew that this story was about to break and yet they didn't find a way to get their website problems resolved in readiness - I think that's pathetic - no commercial organisation could survive with that type of easily resigned attitude.

    This was a big opportunity to raise the profile of ME/CFS in the UK , but I'm not at all convinced that they really want to.

    The guff about the timing of the release of the paper, being the reason why UK news media didn't run with it, is not credible. 48 hrs. have now passed and still virtually no coverage. A more positively minded "can do" advocacy organisation would have had much more success.

    Please prove me wrong. :worried:
  4. garcia

    garcia Aristocrat Extraordinaire

    I'm afraid you are 100% right in your analysis Tgop.
  5. V99


    This story would at least get a paragraph or two in every media outlet. It's pathetic. So why not? Shepherd either doesn't know or cannot say why.

    The media knew about this story since Thursday. It's the usual reasons guys, ignorance, indifference, bigotry and a bit of the psychlobby effect.
  6. Quilp

    Quilp Senior Member

    Please take a closer look at this quote :


    'The MEA continues to believe that the current uncertainty over transmission of these viruses/viral segments means that people with a current or past history of ME/CFS should not be donating blood and we have recently written to the acting Chief Medical Officer at the Department of Health to seek clarification on what appears to be a recent decision to extend the UK ban to people who have recovered from ME/CFS'

    I can barely speak. I want to say so much more, but I can't. If you want to know why we are so poorly represented here in the Uk, please look no further.
  7. Sherby

    Sherby Sherby

    London UK
    Seems strange i would have thought this news would come across excited and hopeful but sounds very down beat to me.
    how can Dr Shepherd say The Lo et al study it is not a true replication study, then how can you say that the four
    emphatically negative validation studies are correct. These cant be validated if your counting them as true replication studies as well. Come on bite the bullet and fight for us the real ME community. Don't talk negative be positive.
  8. V99


    Lo and Alter say that their study and the other 4 were no replication studies, as they used different methodology and criteria. I guess you could say the others were failed validation studies, as they could not detect MLV's, but were they there anyway? Someone should have attempted a replication study by now, and the others should be big enough to admit that theirs were not necessarily up to scratch. Time will tell if this is true. I wish the FDA could also test fresh blood from the CDC patients. Is it the criteria or the collection tubes?
  9. pictureofhealth

    pictureofhealth XMRV - L'Agent du Jour

    That's interesting Quilp. I read this comment as being good for us and the retroviral theory in ME/CFS and that the MEA and DOH are now supporting a total ban on blood donations for us.

    This comment does seem to indicate to me that the DOH do NOT want blood even from people who appear to have recovered from ME/CFS, as well as any one who currently has it, or has ever had it.
    This would suggest, as I take it, that they too may strongly suspect now that CFS is a viral/retroviral infection that you have for life and that they do not want in the UK blood supply.

    Its a big 'about turn' from a few weeks before when it was suggested that we could donate 'provided we were feeling well on the day and feeling up to it' kind of rhetoric.

    I think the MEA want to press the DOH into admitting - 'Well don't donate in case ME/CFS actually is a retroviral infection after all'. I think that's sensible. I certainly don't want anyone else catching this and having to go through all we have been through.

    This is a new development and good for us, as I read it - a total ban on blood donation in the UK for CFS/ME patients and all who have ever been diagnosed with it. In the US I think it is strongly suggested not to donate, but not yet banned and Dr S and the MEA are saying with even the evidence we have now CFS/ME blood donations should be banned in the US, as in the UK.

    Have I missed something? Perhaps its in the wording.

    Roll on the September conference - we need MORE information and more POSITIVE STUDIES.
  10. Marco

    Marco Grrrrrrr!

    Near Cognac, France
    I'm sorry but there's cautious and paralysed.

    I fear the MEA have been around so long the've become part of and cowed by the establishment.

    I'm afraid last year's subscription is likely to be my last.
  11. Quilp

    Quilp Senior Member

    Hello pictureofhealth

    Sorry I didn't make myself clear. Charles shepherd talks of people who have recovered, or had a recent history of M.E. I have never met anyone who has recovered from M.E. I am not saying it's not possible, but the corollary of my argument is that this is a lifelong illness, not something that comes and goes. This is not semantics, this is indicative of a wider ignorance even amongst those that are 'fighting for our cause'. How can we hope to garner wider public support when comments like this feed into the public psyche that this is an illness that will in time 'burn itself out'. It feeds the frenzy of frivolity effusing from those that say, they can cure us. That in turn undermines us further and instead of a heightened awareness of our sufferings, we are left to fight for the very legitimacy of our well being.

    Apologies, Mark
  12. ukxmrv

    ukxmrv Senior Member


    The quote you refer to was from the blood collection agency, they told patients and the MEA that they only wanted blood from "recovered patients" (their words).
    Then a copy of a letter was released that gave us the impression that they were changing the policy to include all patients.

    Dr Shepherd should have put "quote marks" around those words to show that he was quoting them.
  13. Sunshine

    Sunshine Senior Member

    Charles Shepherd needs to make clear who is talking about when he says recovered. Does he mean ME (neuro disease) or the UK Department of Health's CFS/ME biopsychosocial disorder (unexplained chronic fatigue lasting more than 6 months + a few other symptoms?).

    Wessely himself says CBT is not 'remotely curative' for CFS and on ME, he says that doesn't exist. I would like to know from Charles Shepherd how one can 'recover' from ME, a retroviral infection with a disease that causes brain inflammation and massive oxidative stress with no treatment available on the NHS. Maybe there are people who get a lot better with anti viral meds and immune modulators, the problem is we have never seen a documented case yet. Importantly, these drugs are prohibited for use in the UK.

    Even the official figures of 'recovery' from CFS are maxing out at 8%, and these 8% never can do what they previously could with gay abandon with stress still causing relapses, meaning they are not recovered. Dr Bell's recent study showed that people with CFS in America who considered themselves recovered, 50% still qualified for a CFS diagnosis! If Charles Shepherd can show us biological abnormalities when sick in these 'recovered' ME patients, who are now invincible (as before illness) this would be ground breaking research to show the world.

    Charles Shepherd would need to provide evidence of some of the following being present in the now recovered ME patients:

    Inflammatory Cytokines - now normal.
    High IFN - now normal
    High TNF-a - now normal
    High Apoptosis of neutrophils - now normal
    Abnormal Spect/MRI - now normal
    Osteoporosis - now normal
    Reduced core temperature - now normal
    Lowered IQ - now restored to pre illness levels
    Lowered cardiac output on upright TILT - now normal
    Postural Tachycardia/Hypertension/Hypotension - now normal

    Etc etc
  14. Trooper

    Trooper Senior Member

    Totally. One of the biggest.

    They should be maximising attention as we never know when the next one will be.
  15. TomStones


    I find the more established advocacy groups in the in the UK to be very poor at representing M.E/CFS patients. They should have fought the Wessley school argument for argument and allowed the facts to defeat the fiction of the biopsychosocial nonsense. Instead we get very tame press releases from time to time and cosy chats on local radio or whatever. Certainly not enough militancy for my liking.

    When you are being bullied, as we have been bullied by the Wessley school, the only way to put a stop to it is by beating the living daylights out of the bully. The ME association hasn't done that. It has taken all the abuse and hurt and tried to ignore it, thus making the problem worse.

    Perhaps it's time for the gloves to come off and for patient groups to start demanding public inquiries and, in the event of any wrong doing being discovered, long prison sentences for medical fraud and patient abuse. We have been the victims od a dirty war for a long time and it's about time that we learned to fight dirty too. The main weaknesses in any conspiracy of silence are the chain of physical evidence and the very people ionvolved in the conspiracy. In the UK we already have some of the names and we know about the M.E file at Kew. The ME association and other bodies should be going after the files and the people and they should keep at it until something gives.

    Why do i feel the urge to take over the world after a few months of insomnia? :scared::tear:

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