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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Discovery Forum 2017: Dr. Nancy Klimas

Discussion in 'Latest ME/CFS Research' started by Diwi9, Aug 18, 2018.

  1. Diwi9

    Diwi9 Senior Member

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    I don't think this has been posted. Dr. Klimas discusses her modeling of GWI and it has helped her model ME/CFS. She discusses her theories in general with some great visuals and the direction of her research vision of advancing into clinical trials.

     
  2. wigglethemouse

    wigglethemouse Senior Member

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  3. wigglethemouse

    wigglethemouse Senior Member

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    Every time I watch these set of videos I'm just blown away by her confidence and that all that's been holding her back is funding. I can't wait to hear how her GWI trial turns out and then the men and women ME/CFS trials. Has anyone heard anything about the GWI progress? I heard the ME/CFS ones were delayed until later this year.

    Here is a INIM newsletter from the same time period last year - Nov 2017
    INIM_NancyKlimas_Newsletter_Nov2017_1.jpg INIM_NancyKlimas_Newsletter_Nov2017_2.jpg
     
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  4. junkcrap50

    junkcrap50 Senior Member

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    It seems like this presentation was given in 2017, where she said they expect to start the GWI study by "Christmas." Is there any update to the Phase I study of GWI starting by Chritmas she alluded to? It's 8 months after Christmas now.
     
    Last edited: Aug 18, 2018
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  5. Gemini

    Gemini Senior Member

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    Agree @Diwi9 her visuals are great, talk clear and concise! Thanks for posting, worth a watch.

    Studying it for years, here Dr. Klimas presents recent advances in her unified theory of "homeostasis reset."

    An exercise bike, 9 longitudinal blood draws before, during and after exercise challenge, and supercomputers analyzing the "Big Data" gave her a picture of a failure of "anti-inflammatory pathways" in patients. She poses an unanswered question at the moment-- why do they fail?

    Based on treatments tried in her GWI animal studies which reset immune, neurological and endocrine systems, she's moved ahead to a human GWI clinical trial and theorizes the same treatment approach may work in ME/CFS. Like you @junkcrap50 would like to know current status of that trial?

    She suggests two things about potential treatments: go upstream a far as possible towards the cause and address not one but multiple subsystems affected. @alex3619 your thoughts?

    Giving patients helpful advice, one of her last charts [24:00+ on the video] suggests things to avoid and things to do.
     
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  6. junkcrap50

    junkcrap50 Senior Member

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    I wonder if she would have better, faster, or more insightful results of she uses A.I. (artificial intelligence)/Deep Learning and AI-chips (or GPUs) instead of super-computing. It's the latest stuff coming out of Silicon Valley and is supposedly more efficient in pattern recognition and optimal solution seeking. I'm far from an expert, but perhaps someone on here knows more about that field and could provide some insight.
     
  7. alex3619

    alex3619 Senior Member

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    If you were to look at the analysis software I bet many AI techniques would be incorporated.
     
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  8. alex3619

    alex3619 Senior Member

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    These are my take away messages, and not a direct transcript in any way.

    IL-15 restores NK cell cytotoxicity in vitro.

    I started talking about homeostasis and reset decades ago.

    They need modelling because they are not just looking at patterns, they need to predict proximal causation and then predict if an intervention, such as a combination of drugs, will work. This happens in a highly dynamic system. This is much more classical modelling, though very advanced modelling, than a typical AI analysis.

    Some patients were already over their anaerobic threshold before starting exercise and so were disqualified as its too risky to test them.

    First pathways disrupted from exercise in WBCs are immune. The second wave are metabolic, including oxidative stress, sensory and blood pressure regulation.

    Teasing out the pattern of events after exercise might lead to major breakthroughs understanding PEM.

    GWI and CFS are clinically similar, but there are some big differences in the biochemistry. With GWI there is a massive increase in molecular pathways, in CFS there is a massive decrease. To my way of thinking that makes CFS and GWI almost opposites.

    This is about chaos theory to a large extent. I was discussing this in the 90s. The early models I was working with were about homeostasis but based on hormones and hypoxia. These ideas were not advanced very far, and are nothing like the level of complexity we see now.

    A human clinical trial for resetting homeostasis in GWI is due to start soon, based in part on a successful animal model. Funding has been found to do this in ME/CFS. The principle is to inhibit tumour necrosis factor alpha, followed by inhibiting the glucocorticoid response, in a one two fashion. How they create sick animals is give them a toxin, then cortisol, then more toxin, then more cortisol, and they never recover. That is they do not recover until they have their homeostatitic set points reset. That is lower neuroinflammation then lower the cortisol response.

    The proposed trigger is anything that induce neuroinflammation followed by elevated cortisol. This applies to the initial trigger but also relapses.
     
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  9. knackers323

    knackers323 Senior Member

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    @alex3619 The principle is to inhibit tumour necrosis factor alpha, followed by inhibiting the glucocorticoid response, in a one two fashion.

    Do you know how they plan to do this?
     
  10. alex3619

    alex3619 Senior Member

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    I only know what was in the video.
     
  11. wigglethemouse

    wigglethemouse Senior Member

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  12. junkcrap50

    junkcrap50 Senior Member

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    klimas gwi study timeline.png

    I guess we know the status and timeline of study mentioned in the video. If they start it by Christmas 2017, as mentioned in the video. Then, it will be done April 2019.
     
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  13. knackers323

    knackers323 Senior Member

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    Anyone heard of cfsers trying etanercept type meds before?
     
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  14. alex3619

    alex3619 Senior Member

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    I think I have heard of it but do not recall details. The issue here is its not a single medication trial. It requires two different meds in sequence according to the hypothesis.
     
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  15. bertiedog

    bertiedog Senior Member

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    I thought she said in the video that in ME/CFs the glucocortoid response was blunted so why would you inhibit this further? Not sure if she said it was one of the pathways which was opposite to the GWI people.

    This made me wonder if it's the reason I can generally do a lot more than the average ME patient because I top up with a cortisol replacement daily and can feel the effect in my energy level every single time?

    Sorry don't mean to take this off topic.

    Pam
     
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  16. alex3619

    alex3619 Senior Member

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    This is because the entire energy response is altered, and governed by the brain, possibly from a combination of the hypothalamus and the brain stem. She is trying to shift that set point back to normal, and to do that she has to send the right signals to the brain. The details of why this is so in the model would depend on the specific details of the model, and I do not know what they are.

    We know from sepsis research that this kind of problem occurs in severe life-threatening trauma, which in sepsis is often viral. The body rewrites it epigenetic profile. Then the patient either dies or gets better. The survivor then has their epigenetic profile restored ... but a percentage of patients get stuck and never recover. That is suspected in ME. Nancy Klimas has put forward the hypothesis, which is supported by her animal model, that repeated toxin stress (but presumably other things might work) followed by repeated cortisol surges, trigger the problem. Her treatment is aimed at doing the exact opposite to the trigger at the biochemical level. I think that is a very smart first try.
     
  17. junkcrap50

    junkcrap50 Senior Member

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    It's counter-interuitive because she's not trying to support the body's systems, but rather force it to reset it self and find a new equilibrium. Her data suggests that by inhibiting it (at least in GWI, so not necessarily in CFS), you can make the body take on new epigenetic settings, which are back to healthy. You likely inhibit it in GWI because, as she describes in the video, tons of pathways and signals are turned on/sent (opposite of CFS). So you want to stop the over-communication/noise of all those signals.

    Since you seem to be quite knowledgeable, why is there no animal model of CFS? Funding is the likely reason. But I would think some ideas of having an animal model would have been thrown around by now, no? Is it because there's not enough epigentic and metabolomic data available for CFS to confirm the animal model accuracy?
     
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  18. alex3619

    alex3619 Senior Member

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    Animal models of CFS have been put forward but mostly are a joke. One study had animals exercised to exhaustion, and that was supposed to represent CFS! Animal models are also expensive to develop if you want to include any genetic predisposition and so get into genetic engineering. Better models based on monkeys are also very expensive, whereas mice are much cheaper.

    We have lacked both funding and sufficient researcher numbers for so very long.

    There is also the thorny issue that animal models can show a drug works on the animal, and then it usually fails human testing.

    I am a fan of in vitro testbeds, based on samples from real patients, which can then be rapidly tested in many ways without major ethical or health risks. This still does not substitute for real test subjects, but its a way of getting some information and even candidate drugs without risking people.

    Nancy uses a range of things, from models of the biochemistry, to in vitro testing, and now an animal model. Human trials are more advanced, and start with a pilot study, which is mainly about finding if the treatment is plausible by using results in human test subjects.
     
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  19. FMMM1

    FMMM1 Senior Member

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    I haven't watched the video.

    From memory; Ron Davis, in one of his videos, says that animal models can be wrong/misleading. That seems to be a good enough reason to mistrust them.
     
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  20. Belbyr

    Belbyr

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    I'm really impressed with her, I might actually be more impressed with her than anyone else I have listened to discussing CFS. Why that is, is she has accumulated a lot of data that can't be disputed and her success in Gulf War syndrome.

    I am very impressed with the Gulf War syndrome findings. Now I'm anxious to see how the trials are going that are currently under way. If that can be fixed, CFS can be fixed. I think the millions of dollars going towards that illness, as a side effect has significantly helped us out.

    Ron Davis's theory of metabolic trap makes much more sense now. When he says, "once we find the answer, we will have a cure." I believe it.
     
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