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Xmrv research uk

Discussion in 'XMRV Research and Replication Studies' started by joyscobby, Oct 30, 2009.

  1. Dx Revision Watch

    Dx Revision Watch dxrevisionwatch.com

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    Hi parvofighter,

    I hope you won't mind my clarifying that my user name here and the name of my website is "ME agenda" not "MEAction".

    When the UK patient organisation Action for M.E. was first set up it was known as "ME Action" then later had a change of registered name.

    We also have a UK Yahoo! Group list called "ME Action UK" which is run by Stephen Ralph. Stephen maintains a personal website of the same name.

    Neither ME Action UK or ME agenda are any form of organisation and the respective sites are maintained by individuals.

    Suzy
     
  2. Dx Revision Watch

    Dx Revision Watch dxrevisionwatch.com

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    Hi Mark,

    I quite understand why you prefer not to introduce the issue of the content (or lack of content) of the Written Answers received by Paul Rowen MP when following up Dr Shepherd's response; also why you would prefer not to introduce the issue of Des Turner's allusion, at the December APPG on ME meeting, to "promising results from Mill Hill".

    However, since Dr Shepherd's statement:
    is published on the ME Association's website in their position statement

    XMRV and ME/CFS? What do we know so far? And what don't we know?(version 4) (published 27 November)

    and since this has relevance to patient sample selection, and might possibly result in more severely affected patients being excluded from studies that are being carried out using only CDC Fukuda, I consider that Dr Shepherd should be invited to expand on this.

    So perhaps you would give further consideration to requesting a clarification/elaboration from Dr Shepherd?

    If you would rather not - that's fine - let me know and I will ask Neil Riley, Chair of the MEA BoT, to obtain a clarification for me.


    Absolutely.

    Patients and carers, like myself, have waited a long time; we can wait longer. The important thing is to get it right.


    Again, I agree.

    I'll look forward to reviewing your suggestions, Mark.

    Suzy
     
  3. parvofighter

    parvofighter Senior Member

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    My bad!

    Hi ME Agenda,

    I was just coming back to see this conversation, and realized myself that I had botched your name. You're quite right to set me straight. Please accept my apologies!:)

    And keep up the great work. I really appreciate your posts.
     
  4. Dx Revision Watch

    Dx Revision Watch dxrevisionwatch.com

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    Thank you, parvofighter, and I'm glad you weren't offended.

    Suzy
     
  5. Dx Revision Watch

    Dx Revision Watch dxrevisionwatch.com

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    CFS Research Foundation Newsletter

    Prefaced with Notes from ME agenda:


    The Chief Executive of the MRC, Sir Lezek Borysiewicz, is to step down in 2010.

    http://www.meassociation.org.uk/ind...earch-council-to-step-down-in-2010&Itemid=219

    Dr Tim Harrison PhD, DSc, FRCPath. is a Trustee of the CFS Research Foundation and a member of the CFSRF Research Committee.

    Professor Stephen T. Holgate FMedSci, MRC Clinical Professor of Immunopharmacology, University of Southampton is a member of the CFS Research Foundation's Research Committee.

    Professor Holgate chairs the MRC's "CFS/ME Expert Panel".

    Dr Jonathon Kerr is a member of the MRC's "CFS/ME Expert Panel".

    Dr Paul Kellam BSc PhD, Department of Infection, University College London is also a member of the CFS Research Foundation's Research Committee and one of the project supervisors for the UCL PhD Project: Project title:

    A role for XMRV in human disease (http://www.findaphd.com/search/showproject.asp?projectid=18971 ) Division of Infection & Immunity, University College London: Project Supervisors: Prof G Towers; Dr P Kellam



    http://www.cfsrf.com/index.html

    CFSRF Newsletter

    CFS/ME - XMRV Is there a connection?


    It is likely that you will have heard or read about the interesting work being carried out by Dr Judy Mikovits and her team at the Whitmore Peterson Institute in Reno, Nevada to see if the retrovirus XMRV (exenotrophic murine leukaemia virus-related virus) might be associated with CFS/ME.

    This research has been given tremendous coverage by the media throughout the world and while anyone suffering from CFS/ME must feel a degree of excitement we must caution restraint. A good deal more work needs to be done before too many claims can be made as to the relevance of this virus in CFS/ME.

    Recently the retrovirus XMRV was found in the tumour tissue of a subset of prostate cancer patients. Both XMRV positive cancer and CFS/ME have been linked to alterations in a certain antiviral enzyme. The team in Nevada decided to carry out a study to see if this retrovirus might be associated with CFS/ME.

    When the team analysed blood taken from 101 CFS/ME patients 68 ) 67%) tested positive to XMRV genes compared with only 8 (3.7%) out of 218 healthy controls. They stated that their results are consistent with the hypothesis that CFS/ME patients mount a specific immune response to XMRV. The have discovered a highly significant association between XMRV and CFS/ME.

    The research associating XMRV with CFS/ME leaves many questions to be answered. First, it will be necessary for the study to be repeated. Over the years there have been claims for other retroviruses in other illnesses which have come to nought so it is essential that this research is found to have been concluded correctly and for the conclusions reached to be confirmed in independent studies around the world.

    We have to ask the question is XMRV a cause or factor in the pathogenesis of CFS/ME oe a passenger virus in the immunosupporessed CFS patient population.

    Several other viruses have been linked to CFS/ME, for instance the Epstein Barr virus, enteroviruses or herpes viruses, so we must ask what is their relationship to XMRV and the presence or absence off theses viruses.

    Another question must be to ask if the virus XMRV causes CFS/ME or is it just more common in people with the illness.

    In the USA the National Institutes of Health (NIH) have taken this research very seriously. They have called meetings of different departments to discuss the implications of these findings, and they and various groups throughout the world are currently setting out to determine whether this association can be confined for CFS/ME patients in Europe and other countries. They have also made a grant of $2 million to take the research further.

    Dr Jonathan Kerr and Dr Judy Mikovits have been awarded $2 million from the NIH to study the disease mechanisms in CFS/ME. $1 million has been awarded to the research team in Nevada, the other $1 million has bee awarded to Dr Jonathan Kerr at St George's University of London, the scientist well known to all the supporters of the CFS Research Foundation who carried out the research which discovered 88 genes which were abnormal in CFS/ME patients but remained normal in healthy people.

    Dr Kerr will study CFS/ME patients to identify important genes which are turned on and off, proteins in the immune system (cytokines) and mutations in the DNA. Some of these American patients have developed Mantle Cell Lymphoma (MCL) after many years of having CFS/ME; these patients will also be included.

    The CFS Research Foundation tackles some of the questions.


    In spite of the large grant which Dr Jonathon Kerr has received from the NIH the Research Committee has decided that it is imperative that we know if UK and USA patients are infected with XMRV. So the Foundation is to fund a study to establish whether there is a relationship between XMRV and CFS/ME by testing samples from the UK and the USA. Dr Jonathan Kerr and Dr Kate Bishop, who is working at the national Institute for Medical Research in London, are planning to examine patients with CFS/ME and match comparison groups, They will test for the virus itself as well as for the immune responses to this virus. It is of course, vitally important to confirm or refute the finding recently published in the USA.

    The Gene Work Continues


    While this work is causing such excitement the work of gene expression continues. Of the 88 genes which are abnormal in the CFS/ME group but normal in the control group, Dr Kerr found that these genes could be divided into 7 subtypes. What was so interesting was that theses subtypes were associated with distinct differences in their clinical patterns and severity. Each of these subtypes had a different list of genes which were abnormal.

    In a further study Dr Kerr tackled a problem which always causes great concern to CFS/ME sufferers and their families and friends. For years there has been dissension among doctors and scientists as to whether CFS/ME patients were suffering from endogenous depression. Many sufferers felt that this was holding up scientific research. Dr Kerr tested the genes of people with endogenous depression and compared them with the genes of 29 healthy blood donors. Gene levels in the endogenous depressed patients were similar to those in normal controls, but, importantly they are different from the CFS/ME patients.

    Dr Kerr and his team are currently extending the previous findings by including a larger number of well-defined patients. These investigations are being conducted on a blinded basis in order to ensure that there has not been any potential bias on the technical aspects of the study. The samples have recently been collected by Dr Tim Harrison, a Reader in Molecular Virology at University College London Medical School, who visited St George's Hospital to prepare the blinding. The samples were placed in tubes, each one coded, and then frozen. Dr Harrison will keep the code, and no one else will know it until the time set for unblinding.

    You will see that this team will have made sure that their findings are accurate. This contrasts with some previous attempts carried out by other groups on a purely empirical treatment methods that have no firm scientific basis. The research being conducted at the present time by Dr Kerr and his team may well result in not only a reliable diagnostic test but also the initial steps for appropriate therapy based on firm scientific data.

    The Future

    The outlook for CFS/ME research has never been brighter. Increasingly, doctors and scientists are believing that this is an organic disease which need organic research. The paper from Nevada suggesting that the retrovirus XMRV might be associated with CFS/ME has caused great interest and scientists throughout the world have been attempting to repeat this study. Whether or not it is confirmed we already know that virus infection is important in CFS/ME.

    We have some encouraging news from the Medical Research Council (MRC). For years people with CFS/ME, their relations, friends and some research scientists have been frustrated by the MRC's concentration on psychiatrists when conducting research into this illness. This has now changed. The Chief Executive of the MRC, Sir Lezek Borysiewicz is anxious that CFS/ME research should go ahead in a wide field. This must be the best possible news.

    The Foundation is seeking new studies of a high standard. We shall have to re-double our efforts to produce these studies and we hope we can receive some part funding from the MRC. We see the possibility of our research expanding and producing even more radical results as it has in the past. The speed at which we can go forward is up to all of us. We can now look to the future with even greater hope.

    Anne Faulkner, Honorary Director
     
  6. Dx Revision Watch

    Dx Revision Watch dxrevisionwatch.com

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    Testing children?

    Have any of the replication studies that have so far come to our attention going to be testing blood from children and young people? Very little seems to have been said about children in relation to XMRV.
     
  7. Katie

    Katie Guest


    Yes, I would especially be interested in this as I am a childhood onset case myself (11/12 years old) and there are a lot of childhood cases, look at the membership of AYME for starters. My ME has changed so much since I was young and has gone through many different phases. I certainly would not want to be forgotten if I was twelve again and it's a group worth looking at distinctly from adults.

    Nice thought Suzy.
     
  8. Dolphin

    Dolphin Senior Member

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    I heard of one study (not XMRV) where they had difficult recruiting sufficient children. I could well imagine that could be a problem. Also a decent percentage of children might be "short-term" cases e.g. post-glandular fever.

    I have heard ethical permission can be harder to get and/or more work for studies involving children.

    If people are interested in virgins, that could be asked as a question I suppose. Although of course, many under 18 are not virgins either.
     
  9. Dolphin

    Dolphin Senior Member

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    Are you sure that is correct? He has never been on a list I've seen. For example, http://www.cfsrf.com/Staff.htm .
     
  10. Dx Revision Watch

    Dx Revision Watch dxrevisionwatch.com

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    Hi Tom,

    I've just checked back and he isn't currently listed.

    I'll check the "Way Back Machine" and try and establish whether he has been a member of the Research Committee, in the past.

    I note that Dr Tim Harrison is a Trustee as well as a member of the Research Committee, so I'll amend that, too, when I post clarifications - as I've posted this on several lists.

    I'll edit my post above.

    Thanks for spotting this.
     
  11. Dx Revision Watch

    Dx Revision Watch dxrevisionwatch.com

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    @ tomk

    Yes, I understand the ethical issues around research studies and children present barriers to recruitment - did not ME Research UK carry out or fund a study in children a couple of years ago? Vascular??

    But in terms of establishing methods of transmission - I can't quote accurate figures for prevalence in children and young people in the US or UK, but it has been said to be the leading cause of school absence in the UK and the estimated figure quoted by the patient groups is, I believe, 80 - 85,000. I would expect most middle and secondary schools in the UK to have a least one and possibly two or three children with ME at any one time. Several years ago I read of one school that had seven children ill - some not well enough to attend school at all, some attending part-time or for just a few hours a week.

    Thinking about possible methods of transmission: sexual activity; blood; in utero; during delivery; breastmilk; saliva - the rates of association between XMRV and ME and CFS in children and in pre-sexually active young people would be very interesting to be looking into, as would parents of children and YPWME.

    I have not had time to read this thread yet, but I will do:

    XMRV Testing, Treatment and Transmission Talk about test results, treatment options, transmission and personal issues.

    http://forums.aboutmecfs.org/showthread.php?t=642
     
  12. Dolphin

    Dolphin Senior Member

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    Yes, and I heard getting sufficient children turned out to be a lot of work.
     
  13. Dolphin

    Dolphin Senior Member

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    Looking at people who have not been previously sexually active may not be a bad idea with regard to XMRV. But then there are lots and lots of issues with regard to this illness that I think are worthy of study - there have been lots and lots of studies over the years which have found abnormalities that have never been followed up. At least partly because of a lack of money in the field.

    I'm also not sure how one gets at pre-sexually active young people. For example, it could quite a lot of effort asking children about this issue. And might not be suitable really for some. (There can be inappropriate sexual contact). Also prevalence rates get lower the lower the age. It might be simpler if you want pre-sexually active people if you ask for those aged 18 and over who have not been previously sexual active for one reason or another to enroll.

    If XMRV really takes off, I would hope that public agencies might start funding research to study issues regarding the mode of transmission. They'll want to know how it is transmitted. They may be able to study it in animals which might give a more definitive answer.

    At the moment, the pot of money for research that charities can pay for is quite small.
     
  14. Katie

    Katie Guest

    Do you recon people that were virgins when they developed ME might still be of research value even in adulthood? Maybe some gene expression differences or signs of XMRV being there from birth could be still found in adulthood? As I was 11/12 I would fit into that catagory and I have never had a blood transfusion. If I had parent(s) with latent infection that would be interesting also.

    It's a tricky one, but once active XMRV patients can be quickly indentified, patient groups of all ages could be formed quite easily I would assume.
     
  15. Marco

    Marco Old blackguard

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    Follow up questions to Dr Shepherd

    Hi all

    I agreed to collate addtional questions for Dr Shepherd of MEA on the XMRV research. Please feel free to make any suggestions before I e-mail him.


    Dear Dr Shepherd

    Thank you for your response on the MEA's proposals for XMRV related research. I mentioned that I would circulate your response. As you can imagine there is a lot of speculation at the moment with everyone anxious for news.It was well received and I believe provided a degree of reassurance at this crucial time. I also mentioned that there might be some follow up questions or requests for further clarification.

    I have been asked to pass on the following queries if you would be so good to consider them.

    1. Will the MEA be considering XMRV research on :

    (a) the severely affected who are housebound and the most severely affected who are bed bound? It may be difficult to collect the blood, but little seems to be done on researching these groups;

    (b) children and young people? Very little seems to have been said about children in relation to XMRV and it is unclear if any of the proposed replication studies will include them.

    2. According to the summary published by you on behalf of the MEA, following the APPG on ME meeting on 2 December, you stated : It looks as though there may even be some early results from replication studies before the end of the year. Could you please elaborate on this?

    3. In XMRV and ME/CFS? What do we know so far? And what don't we know?
    (version 4) you state that It is worth noting that a significant proportion of people with Ramsay-described ME will not meet Fukuda criteria for CFS - so they are likely to be excluded from research currently taking place. Could you please elaborate on this exclusion?


    Generally speaking, my own view is that the MEA and other patient advocates should not be concerned about being amongst the first to replicate or refute the WPI findings. As you stated, virologists are almost racing to replicate/refute and money doesn't appear to be an issue. I feel the MEA should be concerned with contacting and educating virologists about the likely impact of the various diagnostic criteria on expected findings and monitoring the progress of any research studies in the light of the methodology adopted perhaps this is what you are currently doing? This would go a long way to qualifying the interpretation of any failures to replicate the WPI findings. It appears that a German team have already failed to find XMRV in their CFS cohort although there are suspicions about the assay techniques used, subject selection and even the institutional 'zeitgeist'. Similar problems to what we might expect with UK studies. The role I would see for the MEA at this stage is maintaining an oversight brief if you wish.

    Longer term, as someone so aptly put it, the ME position, vis a vis XMRV, is like the ugly sister being allowed to tag along to the ball. There may be a danger that virologists will be more inclined in the future to research XMRV's involvement in other illnesses such as autism or mantle cell lymphoma which are more easily diagnosed and less 'controversial', especially if early attempts to find XMRV in ME/CFS cohorts have been inconclusive. The MEA should, I believe, be aiming to fund gold standard research and this means using a patient group most likely to represent 'classic organic ME' in other words selected using the Canadian criteria, plus Fukada for comparability and to meet the requirements of the scientific journals. Hopefully also by then the testing methodologies with be refined and standardised. I take your point about the availability of patients but I'm sure a sufficient sample could be obtained by asking for volunteers and assessing them against the Canadian and Fukada criteria.

    Yours etc
     
  16. garcia

    garcia Aristocrat Extraordinaire

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    Bingo! You hit the nail on the head there Mark. IMHO that is *the* key issue. The other stuff is important too, but this is what will make or break the whole issue of XMRV/XAND. Great letter.
     
  17. Eric Johnson from I&I

    Eric Johnson from I&I Senior Member

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    What is the idea in studying children? Only infant subjects can establish vertical transmission. Unless it be gametic vertical transmission of the provirus into the single-cell conceptus, which seems unlikely to me (but I admit I dont know much about it).
     
  18. Katie

    Katie Guest


    Can you write this in layman's terms, I have no idea what any of that means apart from vertical transmission.


    Also, children and teenagers are effected by puberty and XMRV appears to be affected by hormones, it would be prudent to look at XMRV through the pubescent years. It could also be that hormonal changes at the start of puberty may be a factor in activating the virus. Teenagers are also frequently given vaccinations which could be a potential risk factor at their ages, this may need to be addressed. Pre-pubescent child are not so heavily effected by hormonal changes but will do when they reach puberty, there could be differences and lessons to be learnt through them.

    All being said, I'm just a layman.
     
  19. Dolphin

    Dolphin Senior Member

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    I very much doubt many studies will do this. It would mean the trial would be much much more expensive (not sure how many times). Don't think there's that sort of money around. The WPI cohort had done this testing partly because the patients had paid for them as part of their appointment with Daniel Peterson - so perhaps if there was a private doctor that ran such tests, one might be able to do this but generally don't think it's going to happen unfortunately.
     
  20. bananaman

    bananaman

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    From "Invest in ME email"

    Two UK charities are joining forces to fund research into ME/CFS & XMRV

    ME Solutions and Invest in ME are working together to maximise the opportunities to fund research into ME/CFS. The research project is -

    The role of XMRV in modulation of NK cell cytotoxicity and NK cell gene abnormalities in ME/CFS patients and normal blood donors

    The project will be carried out by Dr Jonathan Kerr and his team from St. George's University, London, and Dr Amolak Bansal of the Department of Immunology, Epsom & St Helier University Hospitals NHS Trust.

    Background to the project

    A newly discovered γ-retrovirus, Xenotropic Murine Leukaemia Virus - like virus (XMRV) has recently been found to be present in the blood of 68 of 101 (67%) ME/CFS patients as compared with 8 of 218 (3.7%) normal healthy controls (Lombardi et al, 2009). XMRV has been cultured from T, B and NK cells, but primarily targets NK cells. NK cell dysfunction has previously been found to be abnormal in ME/CFS, despite their numbers often being largely unaffected.

    Defects in the innate immune system are thought to play a key role in the pathogenesis of ME/CFS and these abnormalities may leave individuals susceptible to XMRV infection. This study will relate the presence of XMRV in NK cells with ME/CFS-associated abnormalities previously demonstrated in NK cells and ME/CFS-associated gene abnormalities.

    Plan of Investigation

    A sample of clinically-diagnosed (according to the Fukuda and Canadian criteria) ME/CFS patients and age-and-sex matched normal controls will be recruited. XMRV status will be determined and NK cells obtained and tested for ME/CFS-associated gene abnormalities in NK cells. XMRV status will be related to ME/CFS gene expression changes.

    Donations

    ME Solutions and Invest in ME welcome sponsorship and donations for this two year project which we hope will begin as soon as possible.

    The links below will allow online donations to be made.

    https://charities.everyclick.com/pur...1114035&cy=GBP

    http://www.justgiving.com/mesolutions/donate
     

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