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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. Steve4Andrea

    Steve4Andrea

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    I've got concerns about that, there are multiple postings on PR of disappointing interactions with Montoya's PA's and the Reddit post refers to the PA referring to Sirolimus as an anti inflammatory- Sirolimus does a lot of things but I have not seen it used as an anti inflammatory.

    I am looking at adding Sirolimus to an anti viral protocol and need better confirmation about the interaction, the problem seems to be that Sirolimus is primarily used by transplant Dr.s or Oncologists and they don't seem to have the Infectious Disease background to know how it interacts with anti virals and I haven't been able to find published studies addressing that question.
     
  2. Gingergrrl

    Gingergrrl Senior Member

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    Spoiler Alert: Dumb question ahead... but I am still confused if Sirolimus/Rapamune is used predominantly as an anti-viral or for autoimmunity (or possibly for both)?
     
  3. dreampop

    dreampop Senior Member

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    Or neither - It's being used because some people have found it works. It has a variety of immune modulating and metabolic modulating properties. Given how many changes a drug like this can make, I really doubt anyone can say why it might work, although people will naturally speculate. It is not used as an antiviral, but there are some research articles discussing it - but in very, very specific situations & viruses. It has a potent immuno supressing nature, so it can go the other way, for instance it made flu viruses worse in one paper.
     
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  4. Gingergrrl

    Gingergrrl Senior Member

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    Thank you @dreampop and I appreciate the info. I have been curious about the mechanism of this drug even though it is not something I will be pursuing for myself.

    Would you say that at present there is not one "sub-group" or patient profile of who might be a responder to Rapamune at this time vs. just guesswork? Or is someone autoimmune (or something else?) more likely to be a responder from anecdotal reports?
     
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  5. dreampop

    dreampop Senior Member

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    Honestly, I have no idea.
     
  6. Gingergrrl

    Gingergrrl Senior Member

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    No worries! I have just been curious if the responders to Rapamune fit a certain profile (viral, autoimmune, etc) or if they were a mixture and decided to take it by pure random chance, having no idea if they might be a responder.
     
  7. Steve4Andrea

    Steve4Andrea

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    We are back on the Raqpamune band wagon, today I started my wife on an every other day dose of 1 mg. Rapamune along with her anti viral Arbidol.

    With the posting of the Montoya clinics use of Rapamune I renewed my investigation into using Rapamune with anti viral therapy and found enough info to become comfortable with the usage.

    First- I understand that all viruses are not the same and all anti virals are not he same so what works for one does not work for all.

    I found several studies focused on HIV that did not rely on a population which had received a prior translpant.

    First is this overview of using Rapamune to treat HIV-

    http://pubmedcentralcanada.ca/pmcc/articles/PMC3014061/

    “Theoretically, it may not seem appropriate to use immunosuppressive drugs in HIV-1 infected individuals. However, RAPA exerted a potent antiviral activity in vitro at concentrations lower than those used to cause immunosuppression. Thus, renal transplant recipients receiving daily doses of 2 and 5 mg RAPA achieved trough concentrations of 4.4 nm and 18.9 nm, respectively [53]. When used alone at 1 nm, RAPA profoundly suppressed the replication of R5 strains of HIV-1 in PBMCs with mild antiproliferative effects on cells [40]. This indicates that RAPA doses lower than those used in transplantation may be effective in HIV-1 patients.”

    This led me to this study which evaluated the effectiveness of low dose Rapamune on various cytokines involved in the treatment of HIV-

    http://www.pnas.org/content/100/18/10411.full

    What is interesting about this study is that they evaluated Rapamune at dosages as low as .005mg/day up to 50mg./day. The results are very promising-

    “These results suggest that low concentrations of RAPA may have a role in both the treatment and prevention of HIV-1 infection. “

    I then found research indicating that Rapamune can be effective at reducing IL-10 levels associated with EBV, it is the IL-10 pathway that we believe Arbidol uses to combat the Coxsackie virus although the IL-10 maybe elevated by another pathway than the EBV.

    http://cancerres.aacrjournals.org/content/63/15/4472.long

    The last study I found was a group of 6 MS patients treated with 2mg./day of Rapamune for 6 months and who had 12 different cytokines monitored before and after. This group was chosen for not having existing infections or prior use of steriods. The end result was a minimal effect on the cytokine levels, the significant changes were all to the positive for fighting viral infections.

    http://iji.sums.ac.ir/article_16665_f83547dab1399dc9fa70a5c78f7fa04a.pdf

    We will monitor her for signs of side effects and if they show up we will reduce the dosage or stop all together.
     
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  8. adreno

    adreno PR activist

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    From your post I get the understanding that low dose rapamune functions more as an antiviral than an immune suppressor?
     
  9. Steve4Andrea

    Steve4Andrea

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    I an no expert on Rapamune or most things medical but it appears that Rapamune may be a true immune modulator in lower doses, an immune suppressor in larger doses and an anti tumor agent in even larger doses. I've not come across research showing that Rapamune is "deadly" to a virus in normal concentrations but more that it activates or stimulates some path in the immune system against the virus.

    The MS study indicated to me that without the presence of infection or some other immune stimulant the effects of Rapamune on cytokine levels was very minimal, it only does something if something needs to be done. That fits my idea of what an immune modulator would do.

    As an addendum to my prior post here are two abstracts of studies done by a Chinese group on viral myocarditis caused by Coxsackie B3. I would prefer to see the entire studies but the originals are in Chinese so only the abstracts are available. Again they are looking at immune responses to a viral infection.

    https://www.ncbi.nlm.nih.gov/pubmed/18082048

    https://www.ncbi.nlm.nih.gov/pubmed/19099956
     
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  10. XenForo

    XenForo

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  11. Jesse2233

    Jesse2233 Senior Member

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    Any Rapamune updates from anybody?
     
  12. nandixon

    nandixon Senior Member

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    I'd like to try it now given the work Mark Davis recently presented on CD8 T cell clonal expansion in ME/CFS (see, e.g., this thread). If his work is correct then rapamycin (aka sirolimus or Rapamune) may possibly be helpful to reduce that expansion/proliferation process (assuming that's desirable). (Rapamycin also has other effects besides anti-proliferative with respect to CD8 T cells as well.)

    I think the risk/reward to use rapamycin is okay for my own personal health situation in order to at least do some preliminary testing with it, but I may try to limit it to the weekly dosing approach (see, e.g., this study). It should be apparent pretty quickly whether it will be helpful or not, I think.

    If anyone has found a good source for rapamycin/sirolimus please PM me.Thanks!
     
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  13. Jesse2233

    Jesse2233 Senior Member

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    @nandixon much luck to you! looking forward to hearing your results
     
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  14. Jesse2233

    Jesse2233 Senior Member

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    Here's an interesting study on rapamycin use in uveitis, an inflammatory eye disease.

    Seems that in low doses it makes the disease worse, whereas in high doses the symptoms improve. I wonder what this can teach us on dosing (if anything).
     
    Last edited: Aug 26, 2017
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  15. made_lman

    made_lman

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    I believe it was my post on Health Rising as well as corresponding with a couple of members here that initiated this thread about the use of Sirolimus (Rapamune.) @Jesse2233 asked for an update so here goes. I am continuing to improve after 8 months use (2mg per day) with no noticeable side affects. I am a very long term patient (40 years replaps/remit.)

    Lots of viral activity in my life and high titers at various points in my life. All other relapses occurred after a period of sickness or a severe physical exertion. This relapse started after a flu shot in fall 2014. Diagnosed with CFS in the early 90s and subsequently diagnosed by more doctors. Saw Montoya's PA, was on antivirals for about a year, along with LDN (GOOD), then stopped the anti-virals before I started the Sirolimus. Prior to Sirolimus, I was operating on a functional level averaging 1-2.5 In bed 95% of time.

    Definitely housebound and only out if absolutely necessary. Severe PEM if I did do anything remotely taxing. Even a conversation lasting longer than 10 minutes or too much tv, computer, or reading, etc. would prompt a severe crash with many cognitive issues. During a crash I needed dark and quiet, and had a horrible sense of bees buzzing in my head. I've heard others call it wired but tired but this was much worse. My brain was like on fire. I could not carry on a cogent conversation.

    Did not have pain as many do. But did have subtle muscle twitching during bad crashes. Immediately following the start of Sirolimus in January this year, and continuing to this day - the cognitive difficulties are just gone and I have much more energy and can function all day out of bed most days, and enjoy an occasional shopping spree and dinner or a movie out. I function consistently at around a 7-8 now. 10 for me is on the golf course and not quite there yet:( If I don't listen to my body and pace my activities, I still have periods where I have to lie down to rest. BUT the recovery time after overdoing it, is a day or 2, not weeks or even months.

    I am able take care of myself, do light housekeeping, and enjoy reading and art, and working part time on my computer in my business from home. And I have my brain back! I KNEW there was something going on with my immune system because this episode started out like others with light fever, swollen glands, fluish feeling for a few months, but morphed into something quite different - a period of NEVER getting normal sick, even with snotty grandkids and hubby with cold around all the time.

    I believe my immune system was in overdrive which is why I thought to try the mTOR inhibitor, hoping it could modulate what was going on with my immune system. I got the flu within the first week after Sirolimus (along with husband who brought it home) and was really excited about being normal sick. Took a month to recover, and have been steadily improving since. I can not emphasis enough the disappearance of my cognitive difficulties. I hated the PEM because I normally am extremely active when I am well, but thought the brain dysfunction would be the end of me at some point. I just could not accept that part, and certainly could not think my way out of it! I do not follow a particularly stringent diet, I take a really good multivitamin with Metfolin, still take LDN at 5.5 mg, a blood pressure med, and metformin for pre-diabetes. (Both are long term RX) I stopped taking all other supplements about a year into this episode before I tried the anti-virals.

    I am a stickler on one thing at a time to find out what actually works! I did come out of all other relapses within a few weeks or months of rest, but this one was different - long and new symptoms. Since nothing in my regimen changed I am assuming it is the Sirolimus causing the immediate improvement. The LDN had a positive affect on the cognitive but the Sirolimus was like LDN super plus. So... I am interested in the brilliant minds that frequent this forum,and would appreciate continuing the speculative discussions on how the pieces of this Sirolimus puzzle fit together, given the many new studies out now. I would love it if someone could diagram it! Sorry so long but wanted to give as much info so not too many questions.
     
    Last edited by a moderator: Aug 29, 2017
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  16. Jesse2233

    Jesse2233 Senior Member

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    Thanks @made_lman for sharing your story! Great to hear of your substantial improvements. Has your doctor mentioned anything about the other patients using Rapamune?
     
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  17. made_lman

    made_lman

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    HI @Jesse2233. Last appointment his PA promised me more information on the other patients - or at least to give them MY information so they could reach out if wanted - but even after 2 phone follow ups reminding her - nada. I will see Dr. in the next month and will really pin him down. This visit will be based on dosage. I self lowered my doseage but after a week or so had increase in symptoms, but hard to tell if was from overactivity or not. Also went back on the LDN. Everything is very stable right now and I like that. I also went to rheumatologist for follow up on some positives on the ANA cascade. But he repeated and found nothing. Sugar levels are stable and not having anything show up in blood work now that is bothersome so really no obvious side effects at this point.
     
    Last edited: Sep 4, 2017
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  18. Jesse2233

    Jesse2233 Senior Member

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    Wow so your ANA became negative after Rapamune?
     
    Last edited: Aug 29, 2017
  19. Jesse2233

    Jesse2233 Senior Member

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    For those counting we now have 3 reports from

    @XenForo
    @eljefe19
    @made_lman

    all saying they were taken from moderate/severe to mild from Rapamune

    And 1 report from @Steve4Andrea of no effect

    Extremely small sample and anecdotal, but 75% major responder rate so far
     
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  20. made_lman

    made_lman

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    Well technically yes, but I have no evidence of correlation. The rheumatologist (who really knew nothing and did not want to know anything about me/cfs) said his tests were more sensitive and sophisticated and he thought the previous positives were negative...
     
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