Invest in ME Conference 12: First Class in Every Way
OverTheHills wraps up our series of articles on this year's 12th Invest in ME International Conference (IIMEC12) in London with some reflections on her experience as a patient attending the conference for the first time.
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Ampligen and Naviaux's discovery of dauer state

Discussion in 'General ME/CFS News' started by ScottTriGuy, Sep 1, 2016.

  1. ScottTriGuy

    ScottTriGuy Stop the harm. Start the research and treatment.

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    What is the connection, if any?

    Hemispherx is making advances in getting approval in various countries. Could Ampligen play a part in light of Naviaux's finding?
     
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  2. paolo

    paolo Senior Member

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    Ampligen is an enhancer of the antiviral response. It acts through binding to toll like receptor 3 (TLR3) in dendritic cells, and this leads to the activation of the innate immune system response to viruses.

    If a virus is the permanent threat which mantains the hypometabolism described by Naviaux and collegues, then removing that threat could help ending the dauer-like hypometabolism. As only a subgroup of CFS patients may have the hypometabolism sustained by an active viral infection, this may be the reason why Ampligen works only for some of us.

    Many other hypotheses are plausible, I guess.
     
    Last edited: Sep 2, 2016
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  3. ScottTriGuy

    ScottTriGuy Stop the harm. Start the research and treatment.

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    Thanks @paolo

    If I understand correctly, of all the potential viruses that may be triggering dauer, Ampligen, and only Ampligen, will work on a subset of ME patients. (hypothetically of course)
     
  4. paolo

    paolo Senior Member

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    Another possible explanation for the efficacy of Ampligen in a subset of PWME, may be the following one: as Ampligen is a fragment of viral double strand RNA, it induces the immune response typical of an acute viral infection. This might reset the dauer-like hypomethabolism, which starts only after the acute fase of an infection.

    In other words, the positive effect of Ampligen in CFS might not be linked to its anti-viral activity, but might be due to its ability to artificially induce the immune response of an acute viral infection. As the dauer-like hypometabolism is not able to manage an acute infection, our system decides to shut it down, at least temporarly.
     
    Last edited: Sep 4, 2016
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  5. paolo

    paolo Senior Member

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    I think that Rituximab might work because of the same mechanism. The body might recognize the antibody induced B cells death as an acute infection, and consequently might decide to shift from the dauer-like hypometabolism to an acute infection mode.
     
    Last edited: Sep 2, 2016
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  6. paolo

    paolo Senior Member

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    @JaimeS What do you think about the above hypothesis for the mechanism of action of both Ampligen and Rituximab in ME/CFS?
     
  7. Gingergrrl

    Gingergrrl Senior Member

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    That is really interesting theory and I wish I knew enough to comment. My doctor said with RTX, it could kill the autoantibodies so when the B-cells grow back either they grow back antibody-free or the antibodies re-grow and just come back (and no way to really predict which way it will go).
     
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  8. user9876

    user9876 Senior Member

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    I don't think the timing for Rituxiab fits that theory. B cells are wiped out pretty quickly but Rituxumab takes a long time to work. The time delay fits the theory that it is associated with Antibodies as they stay around for a while.
     
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  9. Gingergrrl

    Gingergrrl Senior Member

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    This is what I think is happening, too, although I could not have explained it as well. The hope is that when the new B cells grow back, they are auto-antibody free (vs. them just growing back with the pathogenic autoantibodies as if nothing had happened). Is that your understanding of it too?
     
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  10. Hip

    Hip Senior Member

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    I think the therapeutic effect of Ampligen for ME/CFS can be best understood in terms of clearing viral infection.

    Dr Chia and others believe that a chronic intracellular infection with non-cytolytic enterovirus is likely behind ME/CFS. Ampligen works by activating toll-like receptor 3 (TLR3) in the cell, and once activated, TLR3 triggers the release of interferon and other antiviral responses which destroy the intracellular infection.
     
  11. knackers323

    knackers323 Senior Member

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    @Hip does dr Chia use ampligen as a treatment?
     
  12. Gingergrrl

    Gingergrrl Senior Member

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    To the best of my knowledge he does not use Ampligen and I think there are only four US ME/CFS doctors who use it.
     
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  13. Forbin

    Forbin Senior Member

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    Perhaps two different things are occurring . Something that stimulates the immune system, like an acute infection, might temporarily negate the dauer-response in some way; whereas, by cutting off the source of antibodies, Rituximab may be shutting down a chronic autoimmune state that is somehow keeping the dauer-response active all the time. One would be working (temporarily) by adding an "acute" stimulus, the other (more persistently) by removing a chronic stimulus. Superficially, at least, this seems consistent with the continuing need for Ampligen, whereas the results from B cell depletion seem longer-lived (though not always permanent).
     
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  14. user9876

    user9876 Senior Member

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    I think there is a little hope that when new B cells grow back the memory of the auto-antibody has gone but this will often not be the case because b-cells in the bone marrow and spline don't get killed off and retain memories. Hence the need for maintenance doses of Rituximab. I think Fluge and Mella had a few patients who did get better with no maintenance dose but I think most worsened again and so most people are likely to need a regular doses. I think this is the case with RA.
     
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  15. user9876

    user9876 Senior Member

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    I think we can speculate about a lot of different potential mechanisms. But when we do we need to check with what evidence we know that supports them and if their is evidence that clearly rules them out. I don't know enough about the subject to have any confidence over this. I guess I don't like things like the phrase 'chronic autoimmune state' since it is not very specific but I get what you mean. I would speculate that there could be a state where auto-antibodies bind to cells in some type of way to push some type of switch some kind of change in metabolic state. But I suspect it is more complex in that these are complex dynamic cycles in the body and perhaps (constant) disruption in one part of the cycle (via an auto-antibody) leads to a different equilbria on the metabolic states and hence what they were seeing.

    To me the first thing that needs to be done is replication. And to do so comparing against other illnesses (including any known chronic infections, and people who are sedentary .....)

    Then I think it would be good to try to understand more about the cycle and potential triggering mechanisms and detriggering ones. But I have no idea how anyone would go about doing that.

    I also think tracking individuals with regular tests to see how readings change over time and severity would be really interesting but I'm not sure if it would give us more useful information.
     
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  16. Hip

    Hip Senior Member

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    Thinking off the cuff here: I wonder what a combination treatment of IV interferon and Ampligen would do for ME/CFS patients?

    Dr Chia was able to put ME/CFS patients into full remission using a course of interferon treatment. Some of these patients remained in remission for as long as 14 months, but all patients unfortunately relapsed back into ME/CFS at some point after the interferon treatment, because it would appear that the virus was not full eliminated by the interferon, and so slowly clawed its way back.

    But if you could put someone into full remission first with interferon, and then followed up by taking regular Ampligen, might that Ampligen work to keep the virus in check, so that you remained in full remission, and never relapsed?
     
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  17. Danesh

    Danesh

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    If anyone of you are still following this thread after all these months, can you describe the subset that seem to respond to interferon (and possibly then Ampligen)? Does Dr. Chia treat only ME/CFS patients who show an active infection of certain viruses, such as HHV6 or EB? I was disappointed to hear that the hypometabolism is only found in some subsets.
     

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