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The NIH is launching a new study of mitochondria in ME/CFS

Discussion in 'ME/CFS research news' started by strategist, Jul 1, 2022.

  1. strategist

    strategist Senior Member (Voting Rights)

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    MeSci, Hutan, Arvo and 17 others like this.
  2. Braganca

    Braganca Senior Member (Voting Rights)

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    He clarifies that gene product was discovered to be raised in the ME cohort of the NIH intramural study which will be published by 2023.
     
    Lindberg, MeSci, sebaaa and 10 others like this.
  3. strategist

    strategist Senior Member (Voting Rights)

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  4. lunarainbows

    lunarainbows Senior Member (Voting Rights)

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    How is the WAVE3 gene connected to the mitochondria? The amount of the gene product is raised in ME/CFS patients, and that then influences the mitochondria somehow?

    It seems like more and more researchers are interested in the mitochondria (& looking at muscle function / muscle biopsies) now in ME.. I’m glad that this avenue is being seriously looked at.
     
    DokaGirl, sebaaa, Solstice and 7 others like this.
  5. strategist

    strategist Senior Member (Voting Rights)

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    My understanding is that the link to mitochondria is autophagy (degradation of damaged cellular components) and maybe also organization of the mitochondrial network. It also has various other roles.

    But this is a complicated topic and I may be misunderstanding. I'll have to read more. It's possible that the NIH knows something that we don't.

    PS:

    On further reading, a picture emerges of WAVE3 being part of one of several protein complexes that physically attach mitochondria to the endoplasmatic reticulum. This would also allow mitochondria and the ER to communicate with each other. This has been studied in cancer.
     
    Last edited: Jul 1, 2022
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  6. rvallee

    rvallee Senior Member (Voting Rights)

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    There's truly a first time for everything.

    No, seriously though, this would literally be the first time.
     
    DokaGirl, sebaaa, Solstice and 9 others like this.
  7. paolo

    paolo Established Member

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    Any idea about what tissue the gene expression assay was performed on? Were fat tissue and muscle biopsies included in the NIH intramural study?
     
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  8. John Mac

    John Mac Senior Member (Voting Rights)

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    Wasn't the numbers of patients recruited to this study tiny i.e. around 35 over 5 years?
    If it was as low as that wouldn't finding a significant gene product in such a tiny cohort be highly unlikely?
    Sorry may be talking nonsense but I really don't trust Nath or Walitt.
     
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  9. cassava7

    cassava7 Senior Member (Voting Rights)

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    @John Mac If my memory serves right, the investigators had issued an update to the participants in early 2020 noting that they had found evidence of mitochondrial dysfunction with the Seahorse assay. The number of patients is indeed too low to pinpoint a specific gene, but their results may point towards it possibly having a role in ME/CFS.

    Edit: it is the expression of the gene that is upregulated here; this is not the same as identifying variants of the gene (which is the goal of a GWAS study). I don’t know whether assessing upregulation reliably requires as many patients as for a GWAS, i.e. at least 10.000 patients.
     
    Last edited: Jul 1, 2022
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  10. strategist

    strategist Senior Member (Voting Rights)

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    Increased expression of this protein seems hard to interpret because it's involved in so many different things. But that the NIH is doing a mitochondrial study led by a cancer researcher suggests that they might be thinking that the interaction between WAVE3 and mitochondria is the most promising area. There also is some discussion of developing drugs that target WAVE3 to treat cancer. Maybe that's the kind of drug trials Dr Nath is expecting?
     
    Hutan, sebaaa, Laurie P and 2 others like this.
  11. LarsSG

    LarsSG Senior Member (Voting Rights)

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  12. strategist

    strategist Senior Member (Voting Rights)

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    A bit more information on what the WAVE3 gene does in the cell besides having something to do with mitochondria.

    It's part of a protein family that is also involved in cell movement, which involves restructuring of the cytoskeleton. I'm not entirely sure but believe that cell adhesion and cadherins, Wnt signaling and ephrine-eph signaling are also involved in cell movement according and these have been found to be abnormal in ME/CFS in some studies. Maybe a coherent picture is finally starting to emerge?

    https://www.sciencedirect.com/science/article/pii/S0092867411006520
     
    Last edited: Jul 1, 2022
    Ron, mariovitali, Hutan and 5 others like this.
  13. cassava7

    cassava7 Senior Member (Voting Rights)

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    @strategist Regarding the title of the thread, Brian Vastag incorrectly wrote that the NIH would perform a muscle biopsy; they will only do an “optional biopsy of the skin” for this study. Muscle biopsies were already done during the intramural study.
     
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  14. Hubris

    Hubris Established Member (Voting Rights)

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    If this is the big breakthrough, why only 12 patients? Why not confirm it on all the patients enrolled?
     
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  15. Milo

    Milo Senior Member (Voting Rights)

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    Only 12 patients = pilot study or proof of concept.
     
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  16. sneyz

    sneyz Established Member

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    The answer is usually money when it comes to this disease, but let's hope they're just incredibly confident about the effect size this time!
     
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  17. mariovitali

    mariovitali Senior Member (Voting Rights)

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    Last edited: Jul 2, 2022
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  18. Forbin

    Forbin Senior Member (Voting Rights)

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    Does the WAVE 3 gene have anything to due with the deformability of red blood cells?

    [It's not helping my search that "WAVE 3" is also a television news station in Louisville Kentucky. :rolleyes: ]
     
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  19. Laurie P

    Laurie P Established Member

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  20. chillier

    chillier Established Member (Voting Rights)

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    Last edited: Jul 2, 2022
    Simon M, Lilas, MeSci and 1 other person like this.

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