MEA Ramsay Research Fund to fund new research into the role of transcription factors in ME/CFS

March 31, 2011


The ME Association is very pleased to announce that trustees have approved funding for an important new research study that will be investigating the role of what are called transcription factors in ME/CFS.

The research, which has been thoroughly peer reviewed over the past two months, will be carried out by Dr Abhijit Chaudhuri, Professor Peter Behan, Professor John Gow, Professor Chris Hillier, and Simone Hutchinson at Glasgow Caledonian University.

Dr Abhijit Chaudhuri and Professor Peter Behan are neurologists with an impressive clinical and research involvement in relation to ME/CFS.  Professor John Gow has carried out extensive research into the virology of ME/CFS (enteroviral infection in particular) as well as the role of gene expression in ME/CFS: www.meassociation.org.uk/?p=642

Professor Chris Hillier, who is Professor of Physiology at GCU, is a leading expert in disease mechanisms at a cellular and molecular level in cardiovascular, metabolic and genetic disease, and brings fresh thinking in the area of biotechnology to the ME/CFS research agenda.  Simone Hutchinson will be the research assistant on the project.

Transcription factors are complicated proteins that act at a cellular level. They are released in a cascade fashion following harmful stimuli such as infections, trauma, exposure to toxins and drugs and form a key part of the body's initial defensive response. They also help to regulate gene expression – in simple terms they assist in the process of ‘switching on' genes and the activities they control.

There is already some preliminary evidence suggesting that transcription factor abnormalities are involved in ME/CFS and that interventions aimed at reducing the levels of transcription factors could be of value in reducing key symptoms such as fatigue.

The role of the transcription factor nuclear factor (NF)-kB has recently been investigated in relation to XMRV infection – where activation leads to an  increase in the production of XMRV.  Journal of Virology abstract:  http://jvi.asm.org/cgi/content/short/85/7/3179.

The research being funded by the MEA Ramsay Research Fund will be looking at transcription factors in blood samples obtained from four separate groups.

First are people with well characterised ME/CFS – Professor Behan will be doing the clinical assessments.

Second is a group of healthy controls.

Third are some of the people who were involved in Professor Gow's research into gene expression.

Fourth are blood samples that will be obtained from the CFIDS biobank facility in the United States – because the UK biobank has not yet been set up.

The study is expected to take a year to complete.

If a significant abnormality in transcription factors is confirmed in this study this could well lead onto further research which would look at therapeutic interventions aimed at reducing the activity.

Total RRF funding = approximately £42,000

More information on the work of the Ramsay Research Fund can be found on the MEA website: www.meassociation.org.uk/?page_id=1086

30 thoughts on “MEA Ramsay Research Fund to fund new research into the role of transcription factors in ME/CFS”

  1. Brilliant stuff. Am sure I have said before that Prof Behan diagnosed me in 1983/4 – we need more Prof Behans in Scotland and less Prof Sharpes, though I think Prof Sharpe is now down south? And Dr Chauduri whom I met once, six or seven years ago during a clinical trial, helped me with a question about plasma exchanges for my book. So great to see new biomedical research being done after the utter farce of PACE. Go, Glasgow Caledonian Uni!

  2. It’s not really brilliant I’m afraid. Without strict criteria, nothing will be discovered. The CAA biobank is known to contain a mix of people, and “well characterised ME/CFS” is not a criteria. Nuclear factor (NF)-kB also shows up in depression.

    1. Dr Charles Shepherd

      As I know from past experience JT does not seem to ever approve of anything that the MEA does or tries to achieve.

      So I do sometimes wonder why he/she spends so much of his/her time looking at our website.

      Instead of complaining all the time why not go and set up your own ME/CFS charity?

      In answer to the question: Professor Behan, who is an excellent neurologist, will be assesing all the patients who are included in the study. Some, but not necessariy all, will meet with the Canadian definition and we have asked him to note the ones that do.

      The American biobank samples will contain specimens from people with Fukuda defined CFS.

      Part of the purpose of this study is to compare the results in various groups of patients and controls to see which ones have abnormalities and to what extent these abnormalities correlate with symptoms such as fatigue.

      We all believe that this is a very useful piece of research that could then lead to new forms of treatment.

      Why is this so awful?

      1. Dr Shepherd, you do not know me, so your comments are strange.

        I would have thought you would also require research that used strict criteria of inclusion and a study that has a hope of uncovering something worthwhile. If you claim to represent people, then you have to also listen to them. Or are you only interested in those who agree 100% of the time with you. This is about science, not personal emotions.

        The criteria that this study is using is diagnosis by a CFS doctors. None of those doctors mentioned diagnose according to the CCC.

        Will they be ensuring that those included have PEM? And I don’t mean the new definition of PEM that is an unusual response to exercise. PEM as in abnormal measurable physiological responses to exercise.

        How about funding XMRV research with a CCC cohort. At least that is going somewhere, and is not found in depression.

        The CAA biobank is a mishmash. How will you know who has what. They want everyone and anyone.

        Why should anyone with an interest in this disease accept research that will reveal nothing?

  3. Lot of money. Great project. Nice one guys 🙂

    Any chance of a more layperson’s description though? I mean I know you’ve tried, but still it’s a big project for the Ramsay Fund and I would like to understand more about it, if that’s possible.

    1. Dr Charles Shepherd

      Yes – this is new and complicated molecular medicine we are looking at in this RRF funded study.

      Sorry – don’t have time to do a fuller explanation right now as I’m off to London to spend the day working with Professor Harrington’s group – who are producing a detailed assessment and report into how to make the ESA WCA descriptors fair and effective for people with fluctuating conditions like ME and MS.

      Suggest you google ‘transcription factors’ and have a look at some of the explanations – Wikepedia may have one that is reasonably accurate and easy to understand.

  4. This study will not be able to present the results for anyone with CCC. We are then left with Fukuda criteria which is only socio political construct and describes nothing.

  5. I can’t comment on what criteria Prof Behan uses to diagnose ME in 2011 but in 80s there was no CCC (or Fukuda). Prof Behan treated Ramsay-defined ME patients and his abnormal findings in muscle biopsies and EMGs of Scottish patients are described in Dr Ramsay’s book: The Saga of Royal Free Disease. I still recall being told I had myalgic encephalomyelitis and having no idea what that meant – I was relieved nonetheless to finally have a diagnosis after 15 months of virally triggered illness.

    After JT’s first comment, I looked up CAA bank and I can see it uses both Fukuda and CCC patients. And while I can understand JT’s concerns, I find it almost impossible to believe that the doctors listed above would waste a year of time and money on ‘meaningless’ research. Has all Dr Gow’s gene research been in vain too?

    http://www.meresearch.org.uk/research/projects/genesig.html

    Also, I am curious – and I don’t ask this in a combative way, I just want to know! – is there any research going on anywhere currently that uses only CCC defined patients?

    1. It is hard to believe that these doctors would select patients with a criteria like Fukuda. But it happens frequently. Usually in order to obtain funding. Why can the criteria not be mentioned up front?

      The CAA no longer takes CCC by the way. They are not looking for them, only those who have fatigue.

      If a doctor uses a socio political criteria and not one of inclusion, then yes it will be worthless.

      CCC is currently being used in the Blood XMRV working group and the Lipkin study. The NCI is also using it. XMRV is the future for starting to sort out this mess, and the WPI and co need immediate funding.

  6. Will this work have any relevance if and when XMRV/ MLVrVs are shown to be the underlying problem, because
    after watching Dr. Mikovits’ presentation to the NYAS “Pathogens in the Blood Supply” conference on Tuesday, the prospect of that working out looks increasingly likely ?

    1. No. If CCC is not used and the results are mixed with other criteria. Either way this type of research would have to be conducted again with XMRV positives.

  7. Am not familiar with Dr Lipkin so I googled! This link came up straight away.

    http://www.facebook.com/notes/the-cfids-association-of-america/update-on-xmrv-study-being-led-by-dr-lipkin/10150180845200539

    Is this the study you mean, JT, the one funded by NIAID?

    When asked if using CCC, Dr Lipkin replied: ‘The criteria we’re using are very complex. They include all criteria published for CFS, plus additiional criteria established by the clinicians and laboratorians to identify the group with the highest risk for an infectious agent.’

    I am more confused than ever.

    Also, this is an interesting link in relation to Dr Mikovits’ presentation (which I have still to watch). Again, via the estimable Dr Speedy.

    http://niceguidelines.blogspot.com/2011/04/paralyzing-tactics-used-by-cbt-fanatics.html

    1. In November 2010 the WSJ reported that:

      As a starting point, everyone had to agree on how to define a CFS patient for the purposes of the study. The issue has been highly contentious and Lipkin says they tried to agree to criteria for patient selection that “includes everyone’s viewpoints.”
      http://blogs.wsj.com/health/2010/11/17/gearing-up-for-the-big-search-for-xmrv/

      and in the comments the journalist said the following:

      Amy Dockser Marcus wrote:
      This is Amy Dockser Marcus, the author of the blog item. The study will use the Fukuda and Canadian definitions.
      http://blogs.wsj.com/health/2010/11/17/gearing-up-for-the-big-search-for-xmrv/tab/comments/

      So they are using Fukuda and CCC.

  8. Dr Charles Shepherd

    The MEA believes it is very important to continue to fund a diverse portfolio of research – which is why we are funding (or have recently funded) studies into gene expression, muscle energy metabolism, transcription factors and factors involved in the development of severe ME/CFS, as well as aiming to set up a UK biobank (blood sample bank) this summer and a post-mortem/tissue bank, and doing post-mortem research.

    This is an impressive portfolio for a small research charity and if you look back over the years almost all of the studies we have funded have been published in very reputable peer-reviewed scientific journals.

    We continue to point out that the Ramsay Research Fund is willing to fund good quality research into XMRV but money is not, at present, a problem here in the UK when it comes to XMRV research. Consequently, we have not been asked for any funding by any of the virologists and retrovirologists I am in regular contact with.

    Having said that it should be noted that the UK research community has become increasingly sceptical about the link between ME/CFS and XMRV – with many now believing the contamination hypothesis. My personal view is that XMRV is not going to turn out to be a/the cause of ME/CFS and it is not going to be a diagnostic marker/test – although it is possible that XMRV (in whatever form turns out to be correct) may be more common in ME/CFS. So I think it is extremely unlikely that we will be looking at using powerful and potentially toxic antiretroviral drugs to treat XMRV in people with ME/CFS.

    As someone who has this wretched disease I just want to get to the truth – even if this means that XMRV is not the major missing piece in the ME/CFS jigsaw.

    I’m now away for a few days – so won’t be taking part in any further discussion for a bit.

    1. The MEA should of course fund a range of research that uses specific criteria, and the UK biobank use of criteria would receive the same criticism of the CAAs. But let’s tackle the question of XMRV, for which the MEA has funded no research.

      Dr Shepherd, you say that “…we have not been asked for any funding by any of the virologists and retrovirologists I am in regular contact with.”

      Have you considered contacting other retrovirologists who know better? Surely if you keep going to the same people who hold beliefs that are at odds with the published research you will never get a scientific answer.

      You then say that “the UK research community has become increasingly sceptical about the link between ME/CFS and XMRV – with many now believing the contamination hypothesis.” This is an assumption, and clearly at odds with the published research. If anyone wishes to make a claim that is different they should produce research and publish. That no research exists to refute the association of MRV’s to prostate cancer and ME cannot be skipped over to arrive at a personal preference.

      You then say ” My personal view is that XMRV is not going to turn out to be a/the cause of ME/CFS and it is not going to be a diagnostic marker/test – although it is possible that XMRV (in whatever form turns out to be correct) may be more common in ME/CFS. So I think it is extremely unlikely that we will be looking at using powerful and potentially toxic antiretroviral drugs to treat XMRV in people with ME/CFS.” But what are you basing your personal feeling on? It cannot be the published literature, as no evidence supports contamination. Is it this small group of e virologists and retrovirologists that you are in regular contact with? Can you name them? As for the comments about antiretrovirals, why is that important for association to be disproven? Why mention it? Obviously many antiretrovirals have been shown to be safe for human consumption and are no less toxic than antidepressants that doctors have no trouble in prescribing with evidence for depression.

      Truth is not synonymous with feelings, but can only be uncovered through application of the scientific method. As you have the disease too you should also require that those making personal claims back them up with data. Currently there is nothing that would support a claim of contamination, but there is evidence that this is a human replicating retrovirus that is integrated into the genome of those with ME and prostate cancer.

    2. Dr. Shepherd,
      I find your comments about XMRV both astonishing and premature. I think that you need to study what Dr. Mikovits is saying about the reasons for other groups’ failure to find the virus in her latest presentation, before making such comments. I am led to believe that it will be posted on the NYAS website in the next few days http://www.nyas.org/Publications/Ebriefings/Default.aspx

      1. A research group which includes Dr Johnathan Kerr is clearly not as pessimistic about the role that XMRV plays in ME/cfs as our esteemed representatives in the UK.
        http://www.serendipitycat.no/?p=6101

        How ironic that Dr. Kerr doesn’t now have anything to do with the UK researchers that he used to collaborate with on ME/cfs and is evidently more at home working with an overseas group who are still open-minded about the role that XMRV might play.

  9. Not wishing to be contentious, JT, but Lipkin’s research is using a mix of Fukuda and CCC, this appears to be the same as Behan’s and Gow’s, and yet you are heartily dismissive of Behan and Gow on grounds of criteria!

    Re. XMRV, for what it’s worth, I remain thoroughly open-minded. And I am off now to watch Dr Mikovits’ presentation.

    1. Either Lipkin is using both criteria’s (Fukuda and Canadian) to select patients, which will mean they will all meet the Canadian, or there will be two clear groups of Fukuda and Canadian. That is acceptable.

      The study above is using the CAA biobank that does not know which patients are which, consequently you won’t be able to extrapolate the different criteria.

      The study will also be getting patients selected by Behan and Gow. But using what criteria or criteria’s? Are they going to subgroup? Not all definitions allow for subgrouping. Take the PACE trial that used Oxford criteria first. Using that there could be no patients that could have met the London criteria, and some Fukuda patients would also have been excluded.

      Now Shepherd has stated that Behan is “an excellent neurologist”, but what definitions is he using, or are they using? He then says that “Some, but not necessariy all, will meet with the Canadian definition and we have asked him to note the ones that do” But will you be subgrouping or splitting, and what other definitions will be used?

      There is no reason why this information would not be known at this time and why you cannot state what is happening. If you do not ensure that specific criteria are used the results are useless to all.

  10. My feeling is that we should keep an open mind about XMRV. I am sure that there are researchers out there that would be happy to accept funds for XMRV research – maybe even a real replication study of the Lombardi et al study?

    I am sure that Dr Shepherd is aware from the recent MEA poll on XMRV that there is a great deal of interest in this research from the ME community. So why does he down play the connection with XMRV? Does he not want to know the scientific truth like the rest of us?

    1. I think expectation management is the default mode for any Doctor.

      If true, the XMRV link could just be a small part of a larger puzzle. The chicken and the egg question will yet have to follow.

      I am concerned like many, because I do see several questions going consistently unanswered. I’m keen to see an answer to JT’s concerns about the CAA blood bank. If you take that issue out of the equation, this proposed study would become very exciting to me. The idea of separating patients on the basis of multiple diagnosis criteria is compelling.

  11. … I tried Dr Speedy’s link, but the video content does not work. But I see Dionysus has posted another link, that is coming up. I am desperate now to see this, there is so much buzz about it!

  12. JT makes a good point:
    “The study above is using the CAA biobank that does not know which patients are which (CCC or Fukuda), consequently you won’t be able to extrapolate the different criteria.”

    On another matter, there is a rather Heath Robinson way available to experience the Mikovits Blood Supply presentation. Here is a link to the slides: http://www.mecfsforums.com/index.php/topic,6526.0.html

    And here you can download an audio file (it’s rather quiet for me, but then I have bad tinnitus) (Google will give you a “too big to virus scan” warning) https://docs.google.com/leaf?id=0Bx_mm5f6qDVrODg2OWMyOGYtMWJlMi00ZjI4LTlmMzItOTgzYjYwMzZjZDdk&hl=en&authkey=CLe7goQD

  13. I support the MEA and I think this research project looks promising!

    However, I too would like to see all ME/CFS research at this stage being done on a patient group which fulfills both the Canadian criteria and the Fukuda criteria. We need a narrow definition to get excellent research.

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