End ME/CFS Severe Patient Study Turns to the Mitochondria

Discussion in 'ME/CFS and FM News' started by Cort, Mar 18, 2016.

  1. Cort

    Cort Founder of Health Rising and Phoenix Rising Staff Member

    Open Medicine Foundation Study

    The mantra at the Severely Ill/Big Data study at the Open Medicine Foundation is to follow the evidence where it leads. We don't know exactly what Davis has found or if will be ultimately validated. We do know that something eyebrow raising involving the mitochondria has shown up in the early stages of the Open Medicine Foundation's End ME/CFS Severely Ill study. Something eyebrow raising enough for a mitochondrial expert to join the fold.

    Naviaux- Robert-End-ME-CFS.jpg
    Davis has found abnormalities before but this is the first one, he told me, that has really leapt off the charts. It was orders of magnitude different from normal.

    Whatever the finding is it has apparently lead to a mitochondrial expert, Robert Naviaux, MD, PhD being added to the Open Medicine Foundation's Scientific Advisory Board.

    We've had mitochondrial findings before but not from researchers of his ilk. Naviaux is not a doctor and sometime researcher. He's a full-time mitochondrial researcher. His first paper on the subject occurred about 15 years ago. Since then he's co-authored more than 80 studies on the mitochondria, genetics, metabolism and metabolomics. The metabolomics study that highlighted the possible mitochondrial issue in ME/CFS has been submitted to the Journal of the American Medical Association (JAMA). Publication, if it comes, is hoped for in early spring/summer.

    He runs the Robert Naviaux Laboratory at UC San Diego, and is the founder and co-director of the Mitochondrial and Metabolic Disease Center at UCSD.. He's also the co-founder and a former president of the Mitochondrial Medicine Society, and a founding associate editor of the journal Mitochondrion. This man is steeped in the mitochondria - but he also has an interesting immune side.

    Naviaux trained at the NIH in tumor immunology and natural killer cell biology, and at the Salk Institute in virology and gene therapy. With all that experience he seems perfectly placed to understand the role infection/inflammation may play on mitochondrial issues, should they continue to show up, in ME/CFS. In conversation Ron Davis has suggested that mitochondrial problems with the immune cells could conceivably be driving the immune dysfunction in ME/CFS.

    A busy researcher in a hot field, his joining of the OMF Scientific Advisory board speaks volumes about the possible significance of Davis's recent finding. Naviaux wouldn't sign on if something very intriguing hadn't sparked his interest. One patient reported Naviaux replied to her email.

    Davis has stated that Dr. Nath of the NIH's Clinical Center study has been informed of what they've found.

    The Chronic Fatigue Initiative's Mitochondrial Emphasis

    J Transl Med. 2016 Jan 20;14(1):19. doi: 10.1186/s12967-016-0771-6.Mitochondrial DNA variants correlate with symptoms in myalgic encephalomyelitis/chronic fatigue syndrome.
    Billing-Ross P1, Germain A2, Ye K3, Keinan A4, Gu Z5, Hanson MR6.

    The Chronic Fatigue Initiative's move to the mitochondria recently resulted in a paper published by Maureen Hanson of Cornell University. The study involved sequencing the entire mitochondrial genome of almost 400 ME/CFS patients from five sites across the U.S. It determined whether single or groups of variations in mitochondrial genes or something called heteroplasmy were more common in ME/CFS.

    The study found no evidence of inherited genetic disease or heteroplasmy in ME/CFS but one finding suggested that people whose genome gives them an increased tolerance of oxidative stress may be at reduced risk of coming down with ME/CFS. (The mitochondria produce large numbers of free radicals). ME/CFS patients with a group of variations in some mitochondrial genes also tended to display more joint pain, bloating, chemical or light sensitivity, disrupted sleep and experience more dead/heavy feelings after exercise.

    This study did not suggest that variations in the mitochondrial genome caused ME/CFS but it did suggest that once you have ME/CFS some mitochondrial variations might make it worse. That could suggest that something affecting mitochondrial functioning could be present in ME/CFS.

    One study that found evidence of mitochondrial genetic issues in ME/CFS and other "functional disorders" concluded that the "pathophysiology likely involves broad effects on the autonomic nervous system."

    There's the genetics of mitochondrial disease and then there's mitochondrial functioning. If an autoimmune or some other process is affecting the mitochondria then genetic problems need not be present for a disease to have a mitochondrial basis. The next step for Maureen Hanson and the CFI is to determine if mitochondrial problems caused by an autoimmune or another process are impairing the functioning of immune cells in ME/CFS.


    The mitochondria are finally getting some serious attention in ME/CFS. Mitochondrial problems have been found before in the disease and interest is growing in the subject. Newton recently showed for the first time that mitochondrial disorders can cause fatigue as severe as that found in ME/CFS. She found comparable levels of fatigue in about a third of people with mitochondrial disorders. She suggested that future treatments developed to assist mitochondrial patients may be able to help people with ME/CFS. With results like that and researchers like Naviaux and Hanson in the mix, mitochondrial issues should be getting more attention in ME/CFS.
    Last edited: Mar 19, 2016
  2. IrisRV

    IrisRV Well-Known Member

    Yes! Finally major researchers are following up on energy production issues instead of 'fatigue'! I'd guess that many of us have been thinking mitochondria for a long time. While we may have different hypotheses about the cause or trigger for mitochondrial dysfunction (viral, stress, autoimmune, toxin exposure), most of us understand that what makes us different is something to do with energy production -- which points straight to mitochondria.

    We've had trouble getting mitochonrial experts involved because so far all known mitochondrial disorders are genetic diseases we don't have. Of course that doesn't mean we don't have an as-yet-unknown genetic disorder, or (more likely) an acquired mitochondrial disorder -- something that is entirely unknown at this point. If we hadn't been slapped with the psychosomatic label and the misleading and trivializing name CFS, major mitochondrial experts might have become interested in us much sooner.

    For me, this is the most encouraging news we've had so far.
    Last edited: Mar 24, 2016
  3. weyland

    weyland Well-Known Member

    @Cort I heard a rumor that Dr. Naviaux already has a paper in the works on ME, have you heard anything about this?
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  4. Rosie26

    Rosie26 Active Member

    Very pleasing. We need all the pieces of the puzzle.
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  5. Cort

    Cort Founder of Health Rising and Phoenix Rising Staff Member

    Yes, a paper has been submitted to JAMA recently. I don't know anything about its status. Naviaux is pretty well published though and of course Ron Davis is. Hopefully that will help..Crossing my fingers.

    I just added this to the blog from a patient who emailed Naviaux

    "I have only been working in the CFS world for a year, but we have already made several discoveries that have a chance to offer real hope for people who have suffered for so long. We have a paper in review at JAMA. If it is published, we will have a real start on seeing CFS in a new light, and having real tools for new ways to treat patients as individuals, and not just as a patient with CFS."
    Last edited: Mar 19, 2016
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  6. Cort

    Cort Founder of Health Rising and Phoenix Rising Staff Member

    Why not an epigenetic thingie :) process that whacks the mitochondria or an autoimmune process that targets the mitochondria? Perhaps those are possibilities?
    Last edited: Mar 19, 2016
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  7. IrisRV

    IrisRV Well-Known Member

    Certainly sound like possibilities to me. :) So many possibilities, so little time! Let's hope Davis' discovery shrinks the field so we have some hope of figuring this thing out in my lifetime.
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  8. Hello!

    Hello! Well-Known Member

    Very exciting!
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  9. Gijs

    Gijs Active Member

    Cort, if true, could it be that the ANS overactivity is a compensation reaction to deliver (adrenaline) energy? I think, mitochondria problem is a very very plausible explanation for ME and POTS.
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  10. Cort

    Cort Founder of Health Rising and Phoenix Rising Staff Member

    You're going to love this then. This paper was cited by Dr. Hanson

  11. Snow Leopard

    Snow Leopard Active Member

    I'm becoming increasingly convinced that very severe patients have more than one thing wrong - a genetic risk factor is certainly possible for such subgroups.

    JAMA. Interesting. It has been a long time since I have seen a decent paper on ME or CFS in JAMA!

    I have my own hypothesis about dysfunction of fatty acid metabolism and impaired cellular response to oxidative stress, and which pathways could be involved (I wonder if a certain scavenger receptor is involved?). I am interested to see what they have found in this study!
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  12. tatt

    tatt Well-Known Member

    exciting stuff. Certainly something wrong with my energy production today.
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  13. Cecelia

    Cecelia Active Member

    Can't wait! I hope the mitochondrial work underway can help Dr. Davis's son. Those like him in critical states need a breakthrough quickly. Our whole community would celebrate so if a good treatment comes from this mitochondrial work.
  14. jill neimark

    jill neimark Member

    Sounds interesting. Even so, they'll need to do cell culture studies, then mice/rat/zebrafish (the latter are best)--to transgenically modify the animal so it has the same allele, and then expose it to whatever (virus/toxin), see what happens, and see how to stop the resulting oxidative stress, or upregulation of the wrong protein--or whatever occurs. They could then screen drugs, or try compounds, that if successful, might eventually become drugs. This is a long road :)
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  15. serotone9

    serotone9 Member

    This looks promising for legitimacy and treatments, if nothing else (i.e., a cure). With ME, a successful treatment at this point would have to be considered a de facto cure, however, so let's hope it pans out. Ultimately the problem is probably not per se in the mitochondria (imho), but in the neuroimmune regulation of mitochondrial function, probably triggered by complex interplays between neurohormonal systems and the brain and immune system, and it looks like researchers are getting even closer to zeroing in on these causes. Once again, however, I don't even care if they find the cause as long as they can find a treatment that mitigates the symptoms and restores functionality. Fingers crossed.
  16. Cort

    Cort Founder of Health Rising and Phoenix Rising Staff Member

    Good to see an ME/CFS paper like that in JAMA!
  17. Cort

    Cort Founder of Health Rising and Phoenix Rising Staff Member

    Fingers crossed indeed. Treatments often do come first.
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  18. Lisa Schicht

    Lisa Schicht New Member

    He does...but it was turned down for publishment by the JAMA because he does not have enough subjects..so he is trying to get more funding for Dr. Cheney's patients to be in the study..and or look for a different journal to publish. But it will happen eventually.
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  19. San Diego

    San Diego Well-Known Member

    @Cort Do you know how they measured mito function? i.e.: Did they do muscle biopsies?

    Mine was measured using citrate synthase (a buccal swab) - by a mito specialist. It was found to be 273% above normal, indicating clear mito dysfunction. Unfortunately, the best that could be offered was high dose supplements and symptomatic treatments. Even with all that, I have only worsened over time.

    Fortunately, mito dysfunction is being found in many conditions so the push to solve this issue is gaining ground from many different directions.

    According to the expert I saw, the vast majority of adult mito patients do not fit neatly into one of the named categories such as MELAS. As such, we are dismissed by neurologists, and the mito experts we consult are considered to be quacks who willy-nilly toss about what the establishment considers to be a wastebasket diagnosis-de-jour.

    Ron Davis is one of the best things to ever happen to our community. He’s got the golden triad - brilliance, tenacity, and extreme motivation. I’m just sorry it has come at such a high price to his family.
  20. Cort

    Cort Founder of Health Rising and Phoenix Rising Staff Member

    Actually I believe it was a metabolomics study. My understanding is that it found very, very high levels of a substance which could indicate massive mitochondrial issues are present in these patients.

    I think you're right about mitochondrial research arena - the mitochondria are extremely complex and difficult to understand. A lot more research is needed. If I have this right the metabolomics aspect could point at treatments that might be helpful before we understand what is going on. That's my perception but I don't know what they would be.
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