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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New discovery in POTS (and possible reversal of epigenetic origin)

Discussion in 'Problems Standing: Orthostatic Intolerance; POTS' started by Belbyr, Mar 24, 2017.

  1. Belbyr

    Belbyr

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    I know this is a CFS/ME board, but this is interesting considering a lot of CFS patients have autonomic problems. Some of you may be able to make more sense of this than myself.

    The findings:
    https://insight.jci.org/articles/view/90183

    Easy to understand version:
    Australian researchers have an exciting new study out on epigenetic findings in POTS. It's very complicated, but here's a plain English version of their findings. NET is a gene that makes the norepinephrine transporter (NET) protein. This protein helps our autonomic nerves recycle norepineprhine, a substance that nerves use to send messages to each other. When there aren't enough NET proteins made, less norepineprhine is recycled, and more of it is spilled over into the bloodstream. This increases the overall tone of the sympathetic nervous system, which can lead to POTS like symptoms or can worsen them.

    The Australian researchers found that the NET gene is being "silenced" (not making enough NET protein) in some POTS patients. The study included 9 POTS patients.

    The researchers believe this "silencing" is happening because of a complex epigenetic mechanism. Epigenetic refers to factors that regulate gene expression without an alternation in the gene itself.

    The researchers took white blood cells from POTS patients, which had reduced NET protein, and treated the cells with vorinostat, a medication known to reverse the epigenetic mechanism that was found. When the white blood cells from POTS patients were treated with vorinostat, the NET protein level increased, suggesting that the epigenetic mechanism is treatable!

    Please don't rush out and try to get yourself a dose of vorinostat. It's a serious drug used to treat lymphoma that can cause some pretty bad side effects, and we don't yet know how it would work in POTS patients, if at all. There may be other drugs or non-pharmacological treatments that can reverse the epigenetic mechanism too.

    We have hope that this will lead to more research, and perhaps new treatment options for a subset or all POTS patients someday.

    Speaking of more research... if you've read this far down, we'd like to fill you in on a secret. We're planning an NET epigenetic study for the 2017 annual conference with researchers at three major autonomic labs, because we need NET epigenetic data on a larger group of patients. Details to be posted soon! #ResearchMeansHope
     
    AdamS, Susanna D, mango and 18 others like this.
  2. Navid

    Navid Senior Member

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    Any suggestions of supplements or less dangerous drugs we can discuss with our Dr's? If more comfortable you can PM me.

    Thanks
     
    merylg, keenly and Lolo like this.
  3. Lolo

    Lolo Senior Member

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    AUS
    I am in Australia and the last doctor I went to (January this year) had never heard of POTS. I suspect I have OI.
    And if I was was diagnosed with it I would also rather take supplements or less dangerous drugs.
     
    merylg likes this.
  4. alex3619

    alex3619 Senior Member

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    Lol. 2017. There are doctors who have not heard of POTS. Reminds me of the doc that said to me "ME, what's that?"' I do find that in Australia the hospital docs know about OI, and take it seriously, but maybe not POTS.
     
    ahimsa, merylg and Lissyleigh like this.
  5. NelliePledge

    NelliePledge plodder

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    Interesting yet another lymphoma drug in the frame
     
  6. Lissyleigh

    Lissyleigh

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    When I went into hospital a few years ago displaying severe POTS symptoms upon sitting up/movement no one had a clue what was wrong, they did an ECG, decided my heart was fine and told me I was just stressed. Even the consultant cardio said that. Its scary really, for the 21st centuary. There is a real lack of knowledge about so called functional disorders and it's quite shocking that someone can have such severe symptoms and still be believed to be fine.
     
  7. Belbyr

    Belbyr

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    This was pulled from dysautonomia international, I have no clue of any supplements. I know it is a small study, but this seems to fit the theory that is being applied to CFS/ME. Genetic issue(switch flipped)--->autoimmunity--->mitochondria dysfunction.
     
    merylg likes this.
  8. Sushi

    Sushi Senior Member Albuquerque

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    Vanderbilt has been looking at NET for years but I don't know if their research included the epigenetics aspects. They knew that NET was important though. I wonder where they are with it now?
     
    ahimsa and merylg like this.
  9. aaron_c

    aaron_c Senior Member

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    Thinking out loud:

    Vorinostat is a histone deacetylase inhibitor, meaning that it stops a protein from taking acetyl groups off of DNA. I wonder if this means that B5 might be moderately helpful, as it is the backbone of the "CoA" in "Acetyl CoA"? Acetyl CoA, of course, is our body's (only I think?) acetyl group donor. Come to think of it anything that improves metabolism should help a little, as Acetyl CoA is produced from glycolysis, the beta-oxidation of fatty acids, the degradation of branch-chain ketogenic amino acids, and even acetate and ATP.

    Of course, this stuff would only help to the degree that deficient NET is the problem, and also to the degree that there isn't something else inhibiting NET synthesis, or encouraging NET degradation.
     
    ukxmrv and lafarfelue like this.
  10. Belbyr

    Belbyr

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  11. Belbyr

    Belbyr

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    I believe they found a NET problem but it was only found in 1 patient or something like that... I think this is a little different. Satish Raj will be speaking at the DI conference in about 3-4 months. I'm sure this topic will come up.
     
    Sushi likes this.
  12. Jenny TipsforME

    Jenny TipsforME Senior Member

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    Vorinostat can be used to reactivate latent viruses (probably not brilliant for ME!). Would this be intrinsic to what is making it useful for POTS or would alternatives not be immune system related?

    It is definitely promising that they're getting to turn off the underlying mechanism behind POTS. I'm on bisoprolol and ivabradine to turn down symptoms but these aren't getting to the root cause.

    I also think POTS really aggravates my ME in a vicious cycle, so atm may be best target for improving my overall health. Hopeful :)
     
  13. Jenny TipsforME

    Jenny TipsforME Senior Member

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    Does anyone understand this?
    I thought the Rituximab and vorinostat link was interesting but I definitely don't comprehend this abstract.
     
    alex3619 likes this.
  14. Hip

    Hip Senior Member

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    Very interesting, @Belbyr

    Wouldn't NET involvement depend on the POTS subtype though, with NET deficiency perhaps relating more to the low flow POTS (similar to the hyperadrenergic POTS)?

    In low flow POTS, I read on the DINET forum here that there are two forms, one of which involves NET deficiency:

    • Elevated angiotensin II (almost always exclusively female).
    • Norepinephrine transporter (NET) deficiency (more equal in terms of sexes).
     
    Jenny TipsforME and aaron_c like this.
  15. Belbyr

    Belbyr

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    Yeah, I really have no idea honestly what the differences are of low flow and high flow POTS. I think there has been so many terms created within the POTS that specialists are now saying is not as big of a deal as once believed.

    Vanderbilt thinks hyperadrenergic, hypovolemic, and neuro pots are most likely evident in most if not all cases of POTS after other diseases are ruled out.
     
    Jenny TipsforME and Hip like this.

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