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Naltrexone restores impaired transient receptor potential melastatin 3 ion channel function in NK cells from ME/CFS patients, Cabanas et al, 2019

Discussion in 'BioMedical ME/CFS Research' started by Deleted member 3253, Oct 19, 2019.

  1. Lidia, Anna H, sb4 and 15 others like this.
  2. Trish

    Trish Moderator Staff Member

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  3. Trish

    Trish Moderator Staff Member

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    Abstract:

     
  4. Sunshine3

    Sunshine3 Senior Member (Voting Rights)

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    Strong or long lasting pain. I have severe M.E. but I don't have pain. More subsets I guess.
     
  5. Andy

    Andy Committee Member & Outreach

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    Cohort of eight patients and eight controls. Given all the money they get I wonder when they'll start doing proper sized studies?
     
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  6. TigerLilea

    TigerLilea Senior Member (Voting Rights)

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    Is it just me, or is that description more likely to be someone with FM rather than ME? I get muscle pain but it stops within seconds of stopping whatever I am doing. I don't get the kind of pain that would require pain meds, whereas my S-I-L has FM and requires heavy-duty pain meds.
     
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  7. Mij

    Mij Senior Member (Voting Rights)

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    Taking NTX caused me horrible agitated insomnia. I don't have pain.
     
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  8. Trish

    Trish Moderator Staff Member

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    I have muscle pain all the time, and made worse by using the muscles. I think muscle pain is on the list of common but not necessary MEsymptoms on most definitions.
     
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  9. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    Naltrexone hydrochloride (NTX) acts as an antagonist to the μOR thus negating the inhibitory function of this opioid receptor on TRPM3. Therefore, understanding the mechanism of action for NTX in regulating and modulating TRPM3 channel function in NK cells will provide important information for the development of effective therapeutic interventions for ME/CFS.

    This would only make sense if we think that PWME actually have an immune defect relevant to their symptoms involving NK cells. There seems pretty little evidence for that. I am not sure there is much evidence for opiates being immunomodulatory or immunosuppressant. People who use heroin regularly but otherwise keep well with good nutrition do not have immunodeficiency as far as I know.
     
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  10. There doesn't seem to be any evidence of thermal hyperalgesia in ME (TRPM3 being highly expressed in the sensory system and associated with thermoreception). Also, the fenamate NSAIDs are TRPM* antagonists (mefenamic acid, widely available OTC, being one of the most TRPM3 selective) - wouldn't it be likely that we would have clinical evidence of any substantive association between the fenamates and ME symptoms by now?

    I might just be brain-fogged, and I've only briefly skimmed the full paper, but I just can't see how impaired TRPM3 function alone can be associated with the core symptoms of ME.
     
  11. Milo

    Milo Senior Member (Voting Rights)

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    dr Marshall-Gradisnik made it clear when they published their first study relating to their patch-clamp experiment that they didn’t need high sample size to prove their point.

    This current paper certainly looks like a pilot study, to be followed by larger sample, and accompanied by bigger investments.
     
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  12. dreampop

    dreampop Senior Member (Voting Rights)

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    Isn't heat-intolerance a common symptom of me/cfs for many? Of course it has many causes.

    I admit, although largely ignorant, I have always been interested in the TRPs because of the many strange intolerances pwme have - I think of a patient complainng a touch or vibration causes them distress. And of course, heat.
     
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  13. Andy

    Andy Committee Member & Outreach

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    And I'm still unconvinced by their argument on how small sample sizes are acceptable in their work. The test they are using may be a gold standard, but without testing it on larger sample sizes we don't know that it is safe to generalise the results in the way that they do.
     
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  14. Simone

    Simone Senior Member (Voting Rights)

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    I’ve only skim read this so far, but I’m feeling sceptical. Their stated hypothesis is that the TRPM3 impairment is the underlying mechanism driving the condition. In this study, it sounds like they are saying that naltrexone fixes that impairment:
    Functioning of the ion channel was “restored” not improved. Given that they claim that the TRPM3 channel impairment is the cause of all our symptoms, that sounds like they’re saying that the problem has gone away after naltrexone treatment. Essentially, presenting naltrexone as a cure. But anecdotal evidence suggests that it isn’t a cure. It seems to help some (I’m one of the lucky ones), but others it doesn’t help at all, and some it makes worse. I don’t know too many who would say that they experienced restored functioning with naltrexone.

    I wonder how they would explain the mixed results from naltrexone given this claim that it restores TRPM3 function? If anything, doesn’t this undermine their hypothesis about TRPM3 being the underlying mechanism (because, based on the results of this study, those taking naltrexone would have their TRPM3 channel functioning restored and yet are probably still be symptomatic)?

    Unless I’ve completely got the wrong end of the stick?
     
    Last edited: Oct 20, 2019
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  15. InitialConditions

    InitialConditions Senior Member (Voting Rights)

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  16. Sunshine3

    Sunshine3 Senior Member (Voting Rights)

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    God you'd swear they just discovered ldn and it was brand new... I've no faith in this gang. They are good at blowing their own trumpet I'll give them that. Ldn did not help me, I tried three times starting very low. I fainted at one stage and I've never fainted in my life. So it's certainly not a fix all. They've some brass neck. No wonder Ron Davis and team have steered clear.
     
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  17. Andy

    Andy Committee Member & Outreach

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    Sorry, if the past is anything to go by then it is guaranteed that NCNED will oversell it.

    Groundbreaking huh?

    Peak research? World-leading? "identification of the pathology, developing a screening test and pharmacotherapeutic intervention for ME/CFS"??

    Pivotal? Is it? It's been demonstrated on eight subjects - that isn't proof of it being pivotal for me.

    Maybe, maybe not.

    Their constant "worlds first, ever, bestest, bigly, discovery that will cure everything" hype taints any research results that they put out for me. Compare to Mike VanElzakker in my Q&A with him, who was at pains to point out that anything we discussed about his research was talking about initial, early results and shouldn't be taken as conclusive proof or evidence of anything. Or compare them to Fluge & Mella, who did their best to play down the hype around rituximab. I'd hate to think what it would have been like if NCNED had been in the same position as F&M - there probably would have been headlines around the world that they had discovered the cure.
     
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  18. Sid

    Sid Senior Member (Voting Rights)

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    Naltrexone is one of the few things that we can be 100% sure doesn't work for ME/CFS given how many clinicians prescribe it to our patient population in the States and how many of us have tried it on our own without any major benefit. It's so widely available and cheap compared to something like RTX which needed a huge trial to debunk it.
     
  19. Cheesus

    Cheesus Established Member (Voting Rights)

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    Naltrexone works fantastically for me. I went from being almost as sick as Whitney Dafoe to using my laptop several hours a day, listening to audiobooks, sitting in bright rooms, and holding prolonged conversations in a matter of weeks.
     
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  20. Sunshine3

    Sunshine3 Senior Member (Voting Rights)

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    It definitely helps some but not all of us unfortunately.
     

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