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Intriguing biomedical research outlined in CAA newsletter (Winter 2013)

Discussion in 'Latest ME/CFS Research' started by Bob, Dec 16, 2013.

  1. Bob

    Bob

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    Exploratory research looking for biomarkers involving: genes, viruses, antibodies & auto-antibodies. There are a number of different avenues being explored.

    Check out the ongoing exploratory biomedical research on pages 3-5 in the CAA's newsletter:
    http://solvecfs.org/wp-content/uploads/2013/06/SolveCFS_Winter2013_FINALsmall.pdf

    These researchers seem to be new to the field of ME/CFS. (I'm not familiar with them anyway.)
    It seems to me that the calibre of these scientists will ensure that any promising results should lead to meaningful future research studies being carried out.


    Pages 3-5; sections:

    1. Discovering Biomarkers on Genes
    Patrick McGowan PhD. (Assistant Professor in the Department of Biological Sciences at the University of Toronto at Scarborough.)

    2. Virus Biomarkers
    Eric L. Delwart PhD. (Professor of Laboratory Medicine at the University of California San Francisco and Blood Systems Research Institute.)

    3. Antibodies as Biomarkers
    Stephen J. Elledge PhD. (Howard Hughes Medical Institute in the Department of Genetics at Harvard Medical School.)

    4. Autoantibody Biomarkers
    Michael Cooperstock MD, MPH. (University of Missouri Health System.)
    Madeleine Cunningham PhD. (University of Oklahoma)
    David Kem MD (University of Oklahoma)
    Armin Alaedini PhD (Columbia University)

    5. Biomarker Validation
    Michael Houghton PhD. (Canada Excellence Research Chair in Virology and Professor in the Department of Medical Microbiology & Immunology at the University of Alberta.)
    (Houghton discovered the hepatitis C virus* and was awarded the 2000 Albert Lasker prize.)
    [* I thought that it was Prof Harvey Alter who discovered Hep C, but it seems that they both had a part to play in a complex journey of discovery.]
    Last edited: Dec 18, 2013
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  2. aimossy

    aimossy Senior Member

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    Thankyou for this bob really interesting read!
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  3. taniaaust1

    taniaaust1 Senior Member

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    Exciting read that is.. :)
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  4. Bob

    Bob

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    It's just a PDF file. I've attached it to this post. See if you can download it from this post?

    Attached Files:

    Last edited: Dec 17, 2013
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  5. rosie26

    rosie26 Senior Member

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    Fabulous Bob, thank you, I just went and deleted my above post just before you posted. It was frustrating me too much. Had to power out of my laptop 4 times as laptop was freezing. Will read tomorrow now as starting to get late here. xx
    Bob likes this.
  6. WillowJ

    WillowJ Senior Member

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    These are very interesting research questions, but I'm concerned about the criteria in the Solve CFS biobank. If there is no particular criteria (I have never been able to find that there is) or if the criteria is not specific enough, then it may be difficult to generalize or replicate the results, or to find significant results.
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  7. Bob

    Bob

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    This is the only info I've been able to find so far:
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  8. Bob

    Bob

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    Last edited: Dec 17, 2013
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  9. alex3619

    alex3619 Senior Member

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    They note epigenetic and other unspecified biomarkers of interest. We await large scale validation. How many possible diagnostic markers does this make now? At least four? Interesting times.
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  10. warriormom

    warriormom

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    Madeleine Cunningham PhD. (University of Oklahoma)


    I am intrigued by Dr Cunningham's involvement here. She is a founder of Moleculera Labs at the University of Oklahoma, and is a leading expert on PANDAS. I have a child diagnosed with PANDAS over ten years ago. Another child started her journey toward an eventual ME/CFS diagnosis at almost the same time......
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  11. rosie26

    rosie26 Senior Member

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    I wonder what (Prof, Dr ) Michael Houghton who discovered Hep C virus, thinks he has found that may have relevance for ME/CFS ? Seems confident he has found something.
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  12. Firestormm

    Firestormm Senior Member

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    @Bob

    Are you able to shed any light on the comment made in relation to the following:

    From the newsletter:

    Thanks :)
  13. alex3619

    alex3619 Senior Member

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    There was a Maes paper discussed on here a year or two back that showed we probably have massive levels of auto-antibodies, they just are not the ones that are normally looked for. Further we don't have just one type but many. It may also be the case that the antibody process is what is wrong, and that different patients have different sets of auto-antibodies. That will make conventional investigation, presuming the Maes research is accurate, very hard to do.
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  14. Firestormm

    Firestormm Senior Member

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    OK. I shall go out on a limb here, Alex. I wouldn't trust anything published from Maes or Gerwyn for that matter let alone jointly. There. I said it.

    Anyway, I'd like to read something from Cooperstock (as above). It might be that the comments relate to unpublished stuff I suppose, but it would be nice to know what they looked for and how. It could impact on the Rituximab stuff too I guess or at least be of use to those that are involved it trying to work out why Rituximab is seemingly working for some and not others.
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  15. user9876

    user9876 Senior Member

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    I think there is something I don't get about the auto-antibodies. In reality aren't there just antibodies and some are labelled as auto-antibodies as they bind to or react with your own body rather (or as well as) than a pathogen. So how do you test for an auto-antibody as opposed to a normal antibody. Presumably there is a known set that cause or are associated with known diseases but I don't see how they would be relevant to ME since they suggest other disease. I guess you could test the antibodies against bits of tissue to see if they have an effect but that depends on tissue selection and finding a direct and easy to observe effect. As I understand it an antibody may react with a protein and the combination then may cause a problem elsewhere.

    I also wonder if there could be an antibody that would bind to particular receptors in some people but not others depending on the exact nature of the receptors and peoples underlying genetics. Hence could it be possible to have normal antibodies that react in some people but not others?
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  16. Bob

    Bob

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    I don't have any further information re the specific details. In general terms, it seems that they were looking for some specific brain-related auto-antibodies (that they were perhaps familiar with from non-CFS research) perhaps with a specific model of disease in mind. And they couldn't find them (i.e. there were similar levels of autoantibodies in patients as in healthy controls.) But this only means that they didn't find the autoantibodies that they were looking for. It doesn't mean that autoantibodies don't exist in their samples.

    I don't fully understand the following methodology that the article describes, so there may be more to their study than I am able to understand:
    "...to test blood samples ... for autoantibodies against antigens in a human neural cell line, several specific human brain antigens and to mouse brain and dorsal root ganglion tissue."
    Last edited: Dec 18, 2013
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  17. Firestormm

    Firestormm Senior Member

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    Cheers Bob. Appreciate it.
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  18. Bob

    Bob

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    @Jonathan Edwards is the person to ask.
    My guess is that they test for autoantibodies by searching for all present antibodies (any antibodies that they can detect), and if a patient cohort has a higher level of a specific antibody than a healthy control cohort, and no relevant virus (or similar antigen) is detectable in the patients, then you label it as an autoantibody.
    And like you say, genes may perhaps play a role such that the same (auto)antibody reacts differently in different people, depending on small genetic differences.
    I'm just guessing though. I haven't done much reading on autoimmunity.
    Last edited: Dec 19, 2013
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  19. Snowdrop

    Snowdrop Senior Member

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    I've started to have a look at the first researcher, Patrick McGowan.
    While the research may be fine I would be concerned about the conclusions drawn.
    A lot of his research revolves around early childhood trauma, mental health and how that impacts our genetic makeup.
    I have provided links to a few of the papers below:

    http://www.sciencedirect.com/science/journal/01650270/174/1

    http://www.sciencedirect.com/science/article/pii/S0969996109003817

    http://www.nrcresearchpress.com/doi/abs/10.1139/bcb-2012-0070#.UrHg8yj0DoE

    http://www.frontiersin.org/Journal/10.3389/fpsyt.2013.00110/abstract

    A concept I found McGowan referred to in his research is 'biological embedding'. Here is a definition:

    Biological embedding is the process by which experience gets under the skin and alters human biology and development. Systematic differences in experience in different social environments lead to different biological and developmental outcomes. These in turn influence health, well-being, learning, or behavior over the life course. Research at HELP contributes to our understanding of the process of biological embedding: how early childhood environments work together with genetic variation and epigenetic regulation to generate gradients in health and human development across the life course.

    from Human early learning partnership at UBC

    Also, I couldn't link this directly so here's a copy and paste:
    From: Journal of Neuroscience Methods Sept 2008

    http://www.sciencedirect.com/science/journal/01650270/174/1


    The effects of PH on DNA methylation state

    Abstract

    Assessment of methylation state of DNA extracted from brain is becoming one of the most investigated issues in the study of epigenetics and psychopathology. pH effects in brain are known to affect gene transcription, though pH effects on DNA methylation state are unknown. We demonstrate in vitro using an artificially methylated plasmid that DNA methylation state remains stable, even under extreme pH conditions. Next, using two different genomic regions from human DNA, we assess methylation state from both cortical and sub-cortical brain regions using subjects with varying pH levels. No correlation was found between DNA methylation state and pH. These results suggest that DNA methylation state is stable in post-mortem brain.

    Article Outline

    1. 1. Introduction
    2. 2. Materials and methods
    1. 3. Results
    2. 4. Discussion

    My bad if I repeated anything, I'm getting tired.
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  20. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    Why is that?

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