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Article: Light on ME/CFS I: Bad Reception: A Key to ME Uncovered? The Light Gene Expression Studies

Discussion in 'Phoenix Rising Articles' started by Phoenix Rising Team, Jul 15, 2011.

  1. Phoenix Rising Team

    Phoenix Rising Team

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  2. OverTheHills

    OverTheHills

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    Cort, isn't July' Call it ME' month for articles blogs & posts on PR ? All three of these articles are peppered with 'CFS' as well as ME/CFS. I'd like to see them corrected please.

    OTH:thumbsup:
    PS:added later when less tired: I didn't mean that to sound like an order. I was trying to make a request. Sorry.
  3. Enid

    Enid Senior Member

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    Thanks Cort - pause to take all in but this looks to me stunningly good research and understanding.
  4. eric_s

    eric_s Senior Member

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    I have a bit of mixed feelings regarding the Lights. It looks like interesting research, but they are close to Ila Singh and as long as we don't know what happened there, who is right about XMRV, the WPI or Ila Singh, and why each side did what they did, i don't feel too good about that group there. Sorry if that offends some people, i'm just giving my opinion.
  5. omegaman

    omegaman

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    There seems to be a lot going on here. At first read there seems to be promise here after reading this write up.

    Many questions linger in my mind about the Lights work.

    1) how was there cohort selected? Did they use CCC and or specific parameters measuring PEM?
    2) Have they published results using this testing with regard to MDD and if so what were the results? Similair or differential from ME/CFS?
    3) why is it the Lights are aloud to validate there own work with follow up studies yet the WPI is not allowed to do so? Should there work not have to be replicated by other groups in order to be validated . Why is the XMRV work held to this standard but not the Lights work?
  6. Cort

    Cort Phoenix Rising Founder

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    No problem. I have to go over the
    'month of ME' situation with the board of directors.

    I use various terms for this disorder for couple of reasons - one of which is that in order for articles to get picked up by google search I have to use search terms that it picks up on readily.
  7. Cort

    Cort Phoenix Rising Founder

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    I'm not sure what you mean by 'what happened there'. What happened so far as I can tell is that Dr. Singh made an effort to find XMRV and did not find it. I want to point out that Dr. Singh has been studying XMRV for years - she first entered into XMRV research with the prostate cancer studies, her lab validated the Silverman findings with prostate cancer and then she went onto look for XMRV in CFS. I guess my question is why you would assume that she would do her best to find it in prostate cancer and not in CFS? Her career, of course, would only have been aided by her ability to find XMRV in CFS.
  8. Cort

    Cort Phoenix Rising Founder

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    The cohort was selected by Dr Bateman - who is acknowledged to be one of the best diagnosticians in the business. The test results to me suggested that the cohort did have high degrees of PEM - after all, after exercise their gene expression results after exercise were off the charts relative to the other groups.

    As I remember patients with MDD have had differing results in these tests.

    The Lights work will eventually have to be validated by other groups for it to really take hold. I imagine there's a difference though between looking for pathogens - which is obviously a bit dicier than we knew - and doing more or less standardized gene expression tests.

    No subject has gotten the attention in CFS that XMRV has - at this point I don't think its surprising that the Light work has not been tested by other labs - simply because its not as hot a topic. The fact that they were able to validate their findings using a different group of people was important - and enough to get Pfizer to sign off on a new study - Pfizer apparently believes they are on pretty solid ground.

    I think there is alot of promise here :cool:
  9. eric_s

    eric_s Senior Member

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    I meant when we will know more about the circumstances. Wheter XMRV really exists in the population and wheter it's found in higher levels in ME/CFS than in healthy people. Then we will know if Ila Sing has been right or wrong. If she was wrong, then i think she should have done a better job and collaborated more with groups like the WPI. Also i think she stated after the publication of her study that she thinks XMRV is not associated with ME/CFS. I think she should not have said that at this point. Also i vaguely remember that the WPI was not really happy about how their collaboration with Ila Singh went. I'm really not sure anymore, but i think they almost felt stabbed in the back. So at this point it's impossible for me to really judge who was right and who was wrong, but i see some question marks.

    I don't assume she didn't do her best. I also have no idea why she wouldn't do that or why she does or doesn't do anything. The same is true for the WPI and everybody else. Since the XMRV story started i was never able to understand why a lot of the things we see happen and i don't believe it's possible for me to find out the reasons at this moment. I just take the "facts" and let the rest be white spots on the map. But i think it's true that we have seen a number of rather strange things happen. One thing that i can't understand, not only in her case, is why these groups who don't find XMRV don't look for more exchange with the WPI. I would not submit a negative XMRV paper (but i have never submitted any paper), before checking with the WPI wheter they could find XMRV in my subjects and wheter i would be able to find it in their positive samples. And if there is a discrepancy, i think i would try to find out what the problem with one of the two assays could be. If there is no discrepancy, i would look at the cohorts.
  10. Cort

    Cort Phoenix Rising Founder

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    Dr. Mikovits is listed as a collaborator on the study - so they did work with them. I think a big question mark for a lot of people is other researchers not using the exact methods but this has happened so many times now and with so many groups that I've come to the conclusion that the research community has concluded that if a variety of other methods which have proven to work with viruses do not work then that they believe the original finding is faulty. Since its not being done hardly at all my guess is that its really rare for anyone to exactly duplicate the methods of an original pathogen. I would also guess is that the reason for this is that history has shown that that's not necessary - that pathogens do rather readily show up using different types of test.

    I realize that the WPI feels very differently about that and thankfully we'll see whose right. Dr. Mikovits started her career bucking the establishment, so to speak, and maybe she will again - in an even bigger way. I would be surprised but who knows - they are very confident about their findings.

    I believe, though, that Illa Singh used the tests that she felt were most likely to find XMRV - using what she believed to be improved versions of the original tests plus other tests. SHe may be right and she may be wrong but I find it really hard to question her motives. For one she was already studying XMRV before the WPI paper came out and had already found it - so she had a huge incentive as a researcher to find it again - and in fact she looked for it using from 9-12 different tests per sample. That's a far, far cry from the early studies and their kind of slapdash approach. To me that's the sign of a researcher who is trying to find XMRV - not the other way around.

    I don't know what her degree of collaboration with the WPI was - I'm getting the feeling that there is in general not alot of collaboration between labs - that each lab thinks they know their stuff and pretty they much go from there. Of course there are exceptions and Annette Whittemore has stated that the labs that followed their techniques have found XMRV and it sounded like those publications should be out in the not too distant future.
  11. Enid

    Enid Senior Member

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    Dorsal ganglia rings bells - didn't an autopsy reveal inflamation here - will check which.
  12. Cort

    Cort Phoenix Rising Founder

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    Judith Shapiro noted that Sophia Mirza's autopsy revealed inflammation in the sensory ganglia - which are the dorsal root ganglia (DRG). As I remember she also had inflammation in the brainstem. One paper I read said that once a virus is settled in the DRG and the sensory nerves then it has a pathway to the brain.

    Herpes simplex virus, for instance, established latency in the DRG and when it gets to the brain causes the most severe form of encephalitis known.
  13. Enid

    Enid Senior Member

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    Yes just looked up Cort (slow today) - it's all tying up !. (Inflammation of the whole spinal chord and muscles mentioned on Iime and Meaction who carry the transcript). My own went to full encephalitis at worst. Tantalisingly close this research. Thank you very much for all your hard work in putting this together.
  14. alex3619

    alex3619 Senior Member

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    Hi Cort, I am still fascinated by the Light's research, as I was from March 2009. I have high hopes for it.

    On the issue of other researchers replicating results, I don't think it can be attributed to attention on XMRV. Retrovirologists are not the same group as immunologists and exercise physiologists. They have different labs, different methods, and may even have different grants they can apply for.

    Bye
    Alex
  15. L'engle

    L'engle moderate ME

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    I thought most of us had POTS/OI/trouble standing? The article would seem to indicate only about a third of the people in the study had POTS. Very interesting, at any rate!
  16. eric_s

    eric_s Senior Member

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    When reading this article this came to my mind: Shouldn't they also try to find out why these receptors are up- or downregulated? Of course it will make people feel better if the pain or inflammation is reduced (and that's important), but couldn't it be that this is rather fighting the symptoms than fighting the cause of the symptoms? For example, if a virus was causing the problems, couldn't the inflammation be a necessary reaction to at least try to fight the virus, even if not fully successfully? Or couldn't the pain be there because there is some other, underlying problem, like you said here?
    And stopping the pain would be a good thing, but then going back to full activity might actually lead to damage, because the underlying problem is still there and the body is now functioning at a level that is too much.

    I'm only a layman and don't have any qualifications in that area, but unless a dysfunction of these receptors is the cause of ME/CFS, adressing only the receptors would not be the solution, in my limited understanding, or am i missing something? What i find more interesting here is the potential for a biomarker and the possibility to define subgroups.
  17. Cort

    Cort Phoenix Rising Founder

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    Study results are actually quite variable - some show alot of POTS - some show not much in CFS - it's kind of bewildering...
  18. Cort

    Cort Phoenix Rising Founder

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    I agree Eric and you'll probably love Part II - which describes why the Lights think this receptor upregulation is happening. It involves neural centers just outside the spinal cord called the dorsal root ganglia that are highly susceptible to herpesvirus infections (and other viruses including retroviruses). The dorsal root ganglia relay sensory information from the body to the spinal cord and are suspected in playing a role in several neuropathic disorders. The Lights also think they are scrambling sympathetic nervous system activity - resulting in muscle acidosis and other problems.

    So yes, a virus could be causing the problems and muscle acidosis could be figuring in there as well - they would all need to be taken care of.

    Part III deals with a specific virus Shapiro thinks has attacked these nerve centers.
  19. LaurelW

    LaurelW Senior Member

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    I think some of us have OI without POTS. I know I do.
  20. valentinelynx

    valentinelynx Senior Member

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    Pardon me if this shows ignorance of something that has been previously demonstrated, but I am puzzled. How does propranolol, which blocks activities of the sympathetic nervous system (preventing elevation of heart rate and constriction of blood vessels are two important ones) help people who "had decreased (this is not a typo: not increased, but decreased) sympathetic nervous system receptor activation"? I think I've seen this reported before, that beta blockers help POTS, but I don't understand why. I completely get why midodrine would help: by increasing blood vessel tone to return blood to the heart and brain. But propanolol does pretty much the opposite. Anyone in the know?

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