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mTor Inhibitor Rapamune Helps 5 ME/CFS Patients in Dallas

Discussion in 'Antivirals, Antibiotics and Immune Modulators' started by Jesse2233, Apr 6, 2017.

  1. Tunguska

    Tunguska Senior Member

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    Berberine is a little alarming, it's used in the diabetes research and its mechanism is this other part that your link happens to mention: "In view of the evidence that BRB localizes in mitochondria, inhibits respiratory electron chain". They know it as a mitochondrial inhibitor.
    [No comment on rapamycin, perfectly plausible it helps in one way, not to mention people have gotten symptom relief from mTor inhibitors all the time]
     
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  2. Jesse2233

    Jesse2233 Senior Member

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    Fair enough! Will be following your progress
     
  3. nandixon

    nandixon Senior Member

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    Assuming that Rapamune (sirolimus aka rapamycin) does turn out to be beneficial for a number of people, I don't think there's much chance that this means mTORC1 is actually over-activated in ME/CFS. I'm definitely sticking with it being under-activated/inhibited.

    A couple of explanations for why rapamycin might be working are:

    1. Perhaps under-activation of mTORC1 in ME/CFS is actually a beneficial adaptation of the body in its attempt to deal with the disease and further inhibition of mTORC1 by rapamycin is helping achieve this goal.

    2. Perhaps there is some non-mTORC1 related beneficial effect that rapamycin has that outweighs the seemingly negative effect of inhibition of mTORC1.

    Regarding #1, a mouse study found that rapamycin was able to protect cardiac function in a sepsis model by further reducing mTORC1 activity that had already been reduced upon pathological exposure to lipopolysacharride (LPS). (Not sure if it's just a coincidence here that ME/CFS has been found to closely resemble SIRS/sepsis at the mRNA gene expression level.)

    Regarding #2, even though rapamycin inhibits the mTORC1 enzyme complex it actually increases the activity of the upstream Akt regulator enzyme. (The above mouse study also notes this as well.) This is pretty remarkable because most other substances that might inhibit mTORC1 will usually inhibit Akt too (e.g., metformin). So this might be a key aspect to the beneficial effect of rapamycin, assuming it is actually helping.

    Lastly, I notice that both Mary Adelman (in the original post) and also @XenForo previously found that low dose naltrexone (LDN) is helpful for them. So it's possible that rapamycin may only work for that subgroup of patients. LDN is very toxic to me but I'm very curious how I'd respond to rapamycin. (Note that naltrexone inhibits both mTORC1 and Akt.)
     
    Last edited: Apr 20, 2017
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  4. knackers323

    knackers323 Senior Member

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    @eljefe19 @Jesse2233 or anyone else who knows about this stuff.

    Does plaquenil effect b cells?
     
  5. ljimbo423

    ljimbo423 Senior Member

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    I saw that when I read the paper, and it made my heart skip a beat.;) My experience with Berberine is clearly very positive though. I've been taking it for about 3 weeks now and have worked my way up to 500mg a day. I feel dramatically better!!

    My flu like symptoms are greatly reduced, if fact I usually have a few hours a day, almost every day, where my symptoms are 80-90% gone. Just in general, I feel much better, more energy, more clear-headed, better mood, etc.

    I really think that it's oxidative stress, caused by immune activation, from LPS in the gut that's causing the mito. dysfunction. So my intention is to treat the source of the mito dysfunction, in hopes that will allow them to function normally again.
     
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  6. Tunguska

    Tunguska Senior Member

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    That isn't unheard of though, some AMPK activators can activate Akt like https://www.ncbi.nlm.nih.gov/pubmed/20167101, lipoic acid, etc. It does come up. (sometimes related to others such as mTORC2 but not always, which it shouldn't be for rapamycin)

    Those are plausible ideas, but to me unless rapamycin affects some critical (immune) cell type uniquely, or some other unique effect, it doesn't scream "take me" compared to others (several-day half-life, so unless you can cycle it for this similar to its other applications, longer-term I'd get worried).

    I believe you (and sure my gut is as much a source of problems), it's just that unless it has a truly unique therapeutic effect, I have to believe there are more efficient ways to do that! (that's my theme here)
     
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  7. ljimbo423

    ljimbo423 Senior Member

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    Now you went and did it, got me thinking again!:D
     
  8. Jesse2233

    Jesse2233 Senior Member

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    Not sure
     
  9. XenForo

    XenForo

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    i searched sci-hub for "hydroxychloroquine "b cell" (ablation, depletion)" and couldn't find anything showing plaquenil depleting b cells. But, of course, I might have just missed something or needed to revise my search terms.
     
  10. knackers323

    knackers323 Senior Member

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    I tried it with good early success but had to stop due to it worsening what loijs to be an ear ir tooth infection. Which us proving to be extremely hard to pin down
     
  11. Jill

    Jill Senior Member

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    I wonder why the Dallas dr gave it to their patients ? Any ideas or what tests would indicate the use of it. We have a Dr that will endeavour to try anything within reason on Al, and this med is available in NZ for transplants
     
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  12. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    Interesting.. 30 percent ish of my t-cells are double positive for CD45RA and CDRO. Rituximab didn`t work, so i would be interested in something touching on t-cells. Might not be related though.
     
  13. Jesse2233

    Jesse2233 Senior Member

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    He's a forward thinking oncologist applying his model of the disease with the tools available

    Not sure. Just a stab in the dark but maybe ANA, CellTrend, B-cell count

    Interesting, what tests did you use to determine your T-cell metrics?
     
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  14. nandixon

    nandixon Senior Member

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    It's not clear to me exactly what the nature is of the other 4 patients that Marcia Adelman refers to. Because in a later post in the cited blog she says:

    This sounds like the other patients are either cancer patients or have autoimmune blood diseases - because the doctor is an oncologist and hematologist.

    In either of those cases it might make sense to give the mTORC1 inhibitor Rapamune (rapamycin/sirolimus) since mTORC1 is commonly over-activated in cancers and Rapamune can be very effective in autoimmune cytopenias.

    It would be nice to know how their ME/CFS fits in, timewise, with respect to their other illnesses.
     
    Last edited: Apr 22, 2017
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  15. Jesse2233

    Jesse2233 Senior Member

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    I don't know about the other 4, but my understanding from Marcia's posts is that she's has had atypical relapse remitting ME/CFS for quite a long time
     
  16. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    Jesse don`t know what type of test that is, but I had extensive phenotyping of my b- and t-cells under investigations at the immunological ward at one of the main hospitals in Norway. Had a bone marrow test which also had some weird results, but it could also just be random variation. Nonetheless it has made me suspect there must be something immunological.

    Rapamune was apparantly just finished undergoing a phase 2 for Lupus. They havent published yet
     
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  17. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    Oh and the test result i referred to above was apparently something they were researching at the hospital. They had seen it in a lot of patients with immunological diseases lately, due to the improvement of testing. Last thing i heard they were gonna do extensive genetic testing to see if something comes up.
     
  18. XenForo

    XenForo

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    From Marcia Adelman over on HealthRising.org:
    "The doctor who prescribed Rapamune is my husband’s hematologist. I was too ill to accompany him on his visits so we used FaceTime so I could listen and ask questions about his condition. One day hubbie explained why I was unable to be there and Dr said I should come see him and mentioned treating others with my symptoms with Rapamune with success.

    I knew this relapse was different from others and that for 2 years my immune system was way out of whack and inflammation as result made sense to me given Fluge and Mella research as well as Jarred Younger hypotheses and other researchers writings. Apparently one of this Dr patients came to him with a stack of research asking if willing to work with her with immune suppressant.

    The others he was seeing for other medical challenges but who also had me/cfs. All are improved. This is a very highly respected oncologist in the Dallas area and apparently an outside the box thinker."
    quoted from here:https://www.healthrising.org/blog/2017/03/08/davis-strategic-approach-chronic-fatigue-syndrome/
     
    Last edited: Apr 22, 2017
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  19. XenForo

    XenForo

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    I haven't had time to read them (to see if they're relevant,) but these might be Rapamune / Lupus relevant papers:
    http://twin.sci-hub.cc/5fb0b89abf4342895143b57957ac729f/oaks2016.pdf
    http://moscow.sci-hub.cc/c10cbc4a4fb80a2992fba8426d2e3721/fernandez2006.pdf
    http://www.indianjrheumatol.com/temp/IndianJRheumatol12148-5534497_152224.pdf
    http://twin.sci-hub.cc/b88754aa32d18e79f1afe1de8b70c849/morel2017.pdf
    http://www.jimmunol.org/content/191/5/2236
     
    Last edited: Apr 22, 2017
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  20. Jill

    Jill Senior Member

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    Weird that it's so being used in lupus as so many of us get that similar lupus rash . One dr was convinced al had lupus based on the red rash across his nose but no positive lupus tests. This guy might be onto something . Please please keep us in touch :)
     
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