August 8th, 2018: Understanding and Remembrance Day for Severe ME
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New video from Australia with research summary, etc

Discussion in 'Latest ME/CFS Research' started by Murph, Aug 3, 2018.

  1. Murph

    Murph :)

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    Here's what this video contains:
    Screen Shot 2018-08-04 at 10.53.27 AM.png



    I watched Don Staines at the 7 minute mark. He's from the Griffith University team that does the research on calcium channels etc.

    They have a clear theory that ion channel deficiency is the key, including in the brain and spinal cord.

    I find it plausible - and it has strong explanatory power. It's clear he is on a quite different track to other researchers. But I think that could be a good thing. It's good to dig in multiple places and there could be connections. It's not impossible these ion channel defects could play a part in an immune response, or in prolonging an immune response. Certainly calcium flux is a big part of purinergic signalling, which is Naviaux's theory.

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    Around the 23 minute mark that GP explains how to do a standing test anyone could do at home (excluding Blood pressure measurements) to assess for Orthostatic Intolerance.

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    The physio is an expert in the kind of cardio pulmonary exercise testing they use in research. Seems very good.

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    The immunologist: talks about mast cells, irritants, etc. For mine, not a great speech.

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    Dietitian : did not watch.

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    Q and A. moderately interesting. Staines describes ME/CFS as unique and out on its own rather than being part of a family of autoimmune diseases. I'm a maybe on that. Some similarities to autoimmune diseases are apparent to me.
     
  2. alex3619

    alex3619 Senior Member

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    This is a moderately good video, though I am dubious about the proof of some claims, I do acknowledge that further research might get there.

    The highlights for me were -

    1. Mast cells are found in peripheral blood, they should not be there.
    2. We often have non-allergic rhinitis. This is one of my major problems as it links into more severe breathing episodes.
    3. Exercise metabolism testing shows carb use flatlining and fat use declining dramatically. This clearly shows a metabolic problem with exercise if it can be independently validated.
    4. Be careful spending money on supplements that may not work or may make things worse, get a motorised wheelchair and good internet access. These help you connect with the world.

    I hope NCNED can succeed in their aims, but I am cautious about whether or not the problems are consistent, and whether or not they are primary or secondary. Further research should help answer that, and I look forward to reading it.

    PS I was amazed at the pictures of a patient's feet. Those are MY feet, all the time, and no doctor can explain it. This probably arises because of orthostatic intolerance.
     
    Last edited: Aug 5, 2018
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  3. Gemini

    Gemini Senior Member

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    @alex3619, I've only watched half of the video, haven't gotten to mast cells, but have a quick question:

    Ron Davis' is looking for something in patient's plasma (or missing from it) that can alter cell function? Any possibility it could be mast cell related?
     
  4. alex3619

    alex3619 Senior Member

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    I would think it would be possible, but nothing more can be said than that. Mast cells themselves are too big. It would have to be a released product. The comment on mast cells was almost a one-liner, and I do not know how well its substantiated. I did find it very interesting though, its a line of investigation I have not thought about ... I am not used to thinking of mast cells as migratory or in general circulation.
     
    Last edited: Aug 4, 2018
  5. ljimbo423

    ljimbo423 Senior Member

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    This is the size of the filter Ron Davis used to filter out most of what was causing the cell dysfunction in the serum. This quote is from his wife Janet-

    LINK post #115
     
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  6. Sad Dad

    Sad Dad

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    A little bit off topic, but if you haven't been tested for orthostatic intolerance, please do. It is highly correlated with ME/CFS.

    I certainly can't speak for Dr. Davis, but my understanding is that his current metabolic trap hypothesis is a bit different than this theory.
     
  7. alex3619

    alex3619 Senior Member

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    My current understanding is four metabolic trap hypotheses are being looked at, and probably many more that we are not even aware of. When you don't have certainty in science it often pays to consider all the potentially valid possibilities. The high molecular weight substance is an empirical determination, and until we know what it is or might be not much more can be said.
     
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  8. MEssias

    MEssias

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    very simple question: how should this approach explain the ME outbreaks? These are all more consequences of something infectious !? outbreaks can not be explained otherwise
     
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  9. ljimbo423

    ljimbo423 Senior Member

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    This is the view of Derya Unutmaz, a leading ME/CFS researcher-

    LINK

    Here is a study that also has the hypothesis that an infection could be a trigger for ME/CFS-

    LINK
     
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  10. Gemini

    Gemini Senior Member

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    @alex3619 I too haven't thought about that and like you find it very interesting!

    I listened to Prof. Pete Smith make his comment [about 36.28 on the video] and checked PubMed for two mast cell papers he might have been referring to, but that wasn't too clear on the video:

    https://www.ncbi.nlm.nih.gov/pubmed/27362406
    https://www.ncbi.nlm.nih.gov/pubmed/29223146

    Papers seem to say mast cells circulate in immature form in the circulation and ordinarily not in mature form. Their researchers found activated mast cells in patients and more mast cell progenitor cells circulating in the blood than in controls.

    Interestingly, doing a quick internet search I see that large-scale mast cell degranulation-- cells burst and spill their contents-- can cause "hypovolemia" (low blood volume), hypotension, vascular permeability, and other symptoms. Also "exercise" can trigger mast cell activation. Astronauts get hypovolemia in space which resolves when they return to the gravity on earth; perhaps this is how it occurs in those of us earth-bound!

    So now I'm wondering (1) as you point out Alex whether any mast cell contents might be in the plasma getting through the filter @ljimbo423 indicates Ron Davis used; and (2) whether cytokines Dr. Montoya measured after exercise might have come from mast cell activation due to the exercise.

    Also be nice to know if Maureen Hanson's planned exercise research will include mast cells (she said at the London Conference she'd be looking at immune cells by type) and that Dr. Chia would be collaborating. Could that be to examine the tissue microenvironment where one might find viruses and mature mast cells?

    So many questions and excellent research going on!
     
    Last edited: Aug 5, 2018
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  11. MEssias

    MEssias

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    Unfortunately that does not make sense. or why in an outbreak, by chance, should so many people have the same microbial response to a pathogen? how to turn it and turn it must be a pathogen that is the cause of ME. no gene and no microbiome...
     
  12. Murph

    Murph :)

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    We recently learned a way that infection can screw with our genetics: Research showed EBV infection seemed to increase the risk of autoimmunity by binding to the genes at the exact locations where the autoimmunity problems crop up.

    https://www.nih.gov/news-events/new...ein-can-switch-risk-genes-autoimmune-diseases

    The insight here was that the infection can act as an epigenetic factor, something that switches genes on and off, or in some other way alters gene function.

    So, hypothetically, the genetic problems associated with ion channels that Staines and Marshall-Gradisnik believe they have found could also be triggered by infections.

    (This is pure speculation, but it provides a pathway to answer your question that does not require going via the microbiome, as I don't see a link from the microbiome to ion channel problems)
     
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  13. Murph

    Murph :)

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    Great analysis! I just contacted @profepetesmith on twitter to see if he can tell us more about that finding of mast cells in circulation.
     
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  14. Murph

    Murph :)

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    Where did you hear four?
     
  15. alex3619

    alex3619 Senior Member

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    I think it was in one of Ron's video talks, or a Q and A. The modelling showed four potential traps, and all need to be examined. Its all theoretical. I hope I am not misremembering, that happens sometimes.

    Right now we have lots of data, a few theories, and very little that tells us with any certainty about causation.
     
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  16. Research 1st

    Research 1st Severe ME, POTS & MCAS.

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    RE: MAST Cells detected in CFS patients peripheral blood. Also found in non CFS. My bold.

    Source:
    Mast Cells Cultured From the Peripheral Blood of Normal Donors and Patients With Mastocytosis Originate From a CD34+/Fc6RI- Cell Population
    Menachem Rottem, Tadashi Okada, Julie P. Goff, and Dean D. Metcalfe
    www.bloodjournal.org
    August 5, 2018.
     
  17. Murph

    Murph :)

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    Relevant to Don Staines talk above and maybe quite big news, his team just posted this on Facebook.

    A turning point for CFS/ME Research
    NCNED have announced that a pivotal research publication has been accepted: ‘Loss of Transient Receptor Potential Melastatin 3 ion channel function in natural killer cells from Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients’. This article proves a significant impairment in TRPM3 function in NK cells and that TRPM3 function is significantly compromised in CFS/ME patients. NCNED used the ‘gold standard’ of patch-clamp electrophysiology to demonstrate this world-first discovery.
    NCNED used NK cells as a model for all cells in the body expressing this essential calcium ion channel. TRPM3 calcium ion channels are widely distributed in numerous body systems such as the central nervous system, metabolic and endocrine systems (particularly regulating pancreas and insulin function), cardiovascular system, gastrointestinal system, skeletomuscular system and immune system.
    NCNED are now pursuing additional TRPs they have previously identified in CFS/ME patients and are accelerating drug investigations for pharmaco-therapeutic applications in CFS/ME patients.

    We particularly wish to acknowledge the support of Stafford Fox Medical Research Foundation, Mr Douglas Stutt, the Mason Foundation, the Alison Hunter Memorial Foundation, the Blake Beckett Foundation, McCusker Charitable Foundation, Buxton Foundation, Change for ME Charity, Qld ME/CFS/FM Support Association Qld Inc. and the ACT ME/Chronic Fatigue Syndrome Society.

    Reference: Cabanas H, Muraki K, Eaton N, Balinas C, Staines D and Marshall-Gradisnik S: Loss of Transient Receptor Potential Melastatin 3 ion channel function in natural killer cells from Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients, Molecular Medicine, Accepted 2018.

    Best wishes
    Sonya, Don and the NCNED team
     
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  18. Research 1st

    Research 1st Severe ME, POTS & MCAS.

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    Thanks, don't know if this helps us understand a bit more regarding your post?
    Probably clutching at straws here, but exercise increases core temperature, as does having a hot bath and both make me terrible. 'CFS' is also associated to abnormal heat shock protein production.

    Source:
    Transient receptor potential melastatin 3 is a phosphoinositide-dependent ion channel
    Doreen Badheka, Istvan Borbiro, and Tibor Rohacs
    J Gen Physiol. 2015 Jul; 146(1): 65–77.
    doi: 10.1085/jgp.201411336
    PMCID: PMC4485020
    PMID: 26123195
     
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  19. ljimbo423

    ljimbo423 Senior Member

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  20. Research 1st

    Research 1st Severe ME, POTS & MCAS.

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    Also if I recall correctly there are at least two cases in the non censored UK literature of Dorsal Root Ganglionitis in fatal ME cases. Which explained their sensory problems, such as pain.

    I wonder if somehow the Immune system, via the NK Cells fighting a chronic infection could case a chronic low grade neuroinflammation state leading to this in some patient subsets.

    The Australian researchers work could be very important regarding this matter.
     
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