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ME/CFS: A disease at war with itself
We can all agree that ME/CFS is a nasty disease, particularly in its severe form, but there are abundant nasty diseases in the world. What is unique and particularly confounding about our disease is that so much controversy surrounds it, and not only surrounds it, but invades it too.
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A Neuroinflammatory Model of ME/CFS - Final Part?

Discussion in 'Latest ME/CFS Research' started by Marco, Jul 11, 2013.

  1. leokitten

    leokitten Senior Member

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    Rockville, MD
    Minocycline and doxycycline have also shown to have exert similar effects on glial cell activation and neuroinflammation and unlike Ibudilast they can be easily prescribed. From my understanding until Ibudilast gets FDA approved for an indication here in the US it's nonexistent.
     
    SOC and wastwater like this.
  2. leokitten

    leokitten Senior Member

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    Rockville, MD
    Marco the theory you propose does make sense and I do believe that hyperarousal and sympathetic dominance caused by some underlying factor(s) is key to at least perpetuating this disease (if not causing it) but based on my personal treatment experience I wonder if glutamate is the true source of the problem.

    I know I'm only one data point in the sea of CFS sufferers and last year for a while I thought glutamate excitotoxicity was the culprit and I tried Memantine for a very long time and it did absolutely nothing to improve symptoms or alter disease course, I continued to get worse with worse symptoms. I then tried Amantadine for a long time and it had zero positive effect. During this entire time I have been taking all the other supplements you mentioned, CDP-choline, LDN, NAC, and so many more it's too long to list, you name the supplement I have been taking it every day for more than 8 months and they have had zero positive effect. Things only got worse or at minimum stabilized and didn't get better.
     
    Last edited: Apr 22, 2014
    Sushi and SOC like this.
  3. Marco

    Marco Old blackguard

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    Near Cognac, France
    Hi there.

    I still feel that neuroinflammation plays a central role in ME/CFS and that glutamate/GABA imbalance results but while the recent PET scan study appears to confirm neuroinflammation in ME/CFS we just don't know enough about the mechanisms as yet to know where or with what to intervene. Hence I was careful not to recommend any particular approach but highlighted areas with research potential.

    Re glutamate it may not be elevated levels per se but impaired transport that results in excitotoxic extracellular glutamate and reduced glutamate signalling which could explain cognitive/memory problems. Again - we just don't know and blocking glutamate receptors might just make the problem worse.

    There are often 'paradoxical' effects as well - there's too much interaction and negative and positive feedback loops to be able to accurately predict what is likely to happen. Benzodiazepines are now suspected of causing cognitive decline due to 'neurological kindling' following a glutamate rebound spike while long term opioid use is known to exacerbate neuropathic pain. Blocking pro-inflammatory cytokines 'should' help with MS but I believe that in one study TNF-a blockade (I think) actually sped up demyelination.

    Even in relatively well characterised conditions such as neuropathic pain where neuroinflammation/microglial activation is pretty well accepted and glial inhibition has great therapeutic potential they still haven't cracked it.

    As I'm sure you know microglial activation is a two edged sword - in some circumstances its destructive and in some protective. We really need more research into this area before even thinking of therapeutic approaches - no change is disappointing but symptoms getting worse isn't good at all.

    Frustrating as it is I'd wait for the research.
     
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  4. leokitten

    leokitten Senior Member

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    Rockville, MD
    Marco thank you for the nice response, to be clear NMDA antagonists Memantine (and to a lesser extent Amantadine) didn't seem to make anything worse they didn't do anything at all. I fell ill with ME/CFS not long ago in January 2013 and it was a steady decline in health last year and all that comes with the initial downward spiral of this disease.

    During this time I was aggressively researching and trying anything and everything that made sense to change the disease course and improve symptoms. In the immense arsenal of things I've tried and done, diet changes, pharmaceutical drugs, supplements, the only things that have made some positive difference are the antivirals I'm taking, Valcyte and Famvir. Everything else has just done absolutely nothing it seems... it feels like they just aren't getting to the true root of the problem. Even Valcyte and Famvir I can feel are only attacking a part of my symptoms so I'm still trying new things all the time in order to find what is perpetuating this disease and preventing full recovery.
     
  5. leokitten

    leokitten Senior Member

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    Rockville, MD
    In addition to the antiviral and possible immunomodulating properties of Valcyte, relevant to this thread one reason it may also work in ME/CFS is because it's been shown to be a potent microglial inhibitor, here's recent paper from a group at Stanford:

    Antiviral drug ganciclovir is a potent inhibitor of microglial proliferation and neuroinflammation
    http://www.ncbi.nlm.nih.gov/pubmed/24493798
    http://jem.rupress.org/content/211/2/189.long
     
  6. kangaSue

    kangaSue

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    Australia
    Just touching on the subject of re-purposing of drugs, cilostazol (Pletal) is very similar in action to ibudilast (both phosphodiesterase inhibitors) with the advantage that it already has FDA approval for use as a treatment for intermittent claudication and warrants further evaluation for off label use in accord with the context of Marco's article.
    http://www.onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2009.00615.x/full

    It reduced cerebral hypoperfusion in a rodent model and has been used (albeit in limited application) to treat bowel ischemia (Mesenteric ischemia) in humans, a condition where there are episodes of insufficient blood flow to the bowel causing pain and a large lactic acidosis load. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3284045/

    Similar to the drug that I take for bowel ischemia (Nicorandil), it appears to work in this regard by activating the potassium pathway while selectively blocking calcium influx. http://jpet.aspetjournals.org/content/317/3/1238.abstract
     
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