mTor Inhibitor Rapamune Helps 5 ME/CFS Patients in Dallas

[XenForo]

Xenforo- here are some of the viral studies I've run across, there are numerous citations out there if you search under "Sirolimus viral" (that is the generic name of Rapamune).

http://articles.latimes.com/2014/ap...o-eliminate-lingering-hiv-infections-20140403
http://www.catie.ca/en/treatmentupd...irolimus-potential-applications-hiv-infection
https://www.ncbi.nlm.nih.gov/pubmed/24128134

There is also a sentence in the package insert (https://www.fda.gov/ohrms/dockets/ac/02/briefing/3832b1_03_FDA-RapamuneLabel.htm ) under the paragraph CLINICAL PHARMACOLOGY -Mechanism of Action -

" In some studies, the immunosuppressive effect of sirolimus lasted up to 6 months after discontinuation of therapy."

Oh thanks Steve4Andrea. Hmmm, 6 months effect after discontinuing Rapamune. Here I was surprised about a 1 week continuance. I'll let y'all know how I do.

 

[ScottTriGuy]

Xenforo- here are some of the viral studies I've run across, there are numerous citations out there if you search under "Sirolimus viral" (that is the generic name of Rapamune).

http://articles.latimes.com/2014/ap...o-eliminate-lingering-hiv-infections-20140403

http://www.catie.ca/en/treatmentupd...irolimus-potential-applications-hiv-infection

https://www.ncbi.nlm.nih.gov/pubmed/24128134

There is also a sentence in the package insert (https://www.fda.gov/ohrms/dockets/ac/02/briefing/3832b1_03_FDA-RapamuneLabel.htm ) under the paragraph CLINICAL PHARMACOLOGY -Mechanism of Action -

" In some studies, the immunosuppressive effect of sirolimus lasted up to 6 months after discontinuation of therapy."

Thanks for those links. The HIV studies are particularly of interest to me.

Question (if discussed earlier, please forgive) - if Sirolimus has surprisingly been found to inhibit HIV and HepC, is it possible that the reason its helping ME folks is because its (also?) anti-viral (vs supporting mitochondria)?

 

[Steve4Andrea]

Scott,

There is a lot of HIV info out there, search under Sirolimus instead of Rapamune. It looks like there is a clinical trial starting up as well- ( https://actgnetwork.org/study/a5337-sirolimus-study )

I don't know if we'll ever know for sure but I'm guessing that the rapid improvement with Rapamune for CFS/ME is more immune suppression related rather than anti-viral or mitochondrial, everything I've read about anti-virals says it takes months to make progress against a persistent infection. That said, there may be a long term anti-viral benefit as well with Rapamune, here is a little info on Rapamune and enterovirus-

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

It is hard to separate the studies involving the transplant population with all of their immune suppression problems from the "general" population so I'm not sure what the impact of long term use of Rapamune is for the CFS/ME population. We'll just have to try it and see...

 

[Jesse2233]

I don't know if we'll ever know for sure but I'm guessing that the rapid improvement with Rapamune for CFS/ME is more immune suppression related rather than anti-viral or mitochondrial, everything I've read about anti-virals says it takes months to make progress against a persistent infection. That said, there may be a long term anti-viral benefit as well with Rapamune, here is a little info on Rapamune and enterovirus-

Wow, it seems to be quite the multifaceted drug. If it is delivering benefit via immunosuppression, I wonder how it's fast mechanism of action can be explained vs something like Rituximab which seems to take 3-9 months.

 

[knackers323]

Wow, it seems to be quite the multifaceted drug. If it is delivering benefit via immunosuppression, I wonder how it's fast mechanism of action can be explained vs something like Rituximab which seems to take 3-9 months.

relevent or not im not sure but i had improvement from plaqunil after a week or so

 

[Jesse2233]

relevent or not im not sure but i had improvement from plaqunil after a week or so

What sort of benefits have you seen?

 

[ScottTriGuy]

There is a lot of HIV info out there, search under Sirolimus instead of Rapamune. It looks like there is a clinical trial starting up as well- ( https://actgnetwork.org/study/a5337-sirolimus-study )

Thanks for these links too - the closest trial location is 3 hour drive across the border into the US, I emailed the study coordinator but imagine I will be ineligible because of ME...unless I forget to mention it.

The study of rats with CVB yet another reason I should consider giving it a go as Armin Labs found CVB.

 

[Jesse2233]

I emailed the study coordinator but imagine I will be ineligible because of ME...unless I forget to mention it.

Man I really hope you get it in! Could be a repeat of Fluge / Mella's accidental Rituximab discovery

 

[knackers323]

What sort of benefits have you seen?

i felt much better. after the first tablet i felt a big reduction in the overwhelming heavy exhaustion.
a week later i felt light and something like normal, could move and do things without any effort. afetr feeling like we do, once you get a taste of normal again, you realise youve forgotten how easy everything is when healthy.

i went for a couple of easy jogs with no payback. depression obviously lifted. could see clearly again etc.

then it must have dropped my immunity too low and i began to get a sore ear, which day by day spread to the side of my face, into my teeth, to the other ear, ended up being run down and sleeping for 2-3 days so i stopped and recovered to baseline. pain went away.

tried the plaqunil 2 more times and the pain/infection came back quicker each time.

ive now been trying to find the infection.

ive had a sometimes painfull ear for a couple of years and been to many drs and specialists for it and theyve assured me that there is no infection there.for whatever their assurance means.

so ive looked at a possible infection in the teeth. first dentist immediatly ruled it out. i pressed him to do an x-ray or some sort of investigation. he did an x-ray and said there is possibly a small cavitation in the back tooth on the side of the original painfull ear. but he doesnt think so.

haha. well good thing we did the x-ray hey. these "professionals" dont instill a hell of a lot of confidence.

so now im in the process of trying to work out finding if there is an infection/cavitation there or not.

i didnt think there was any other health issue as difficult to deal with as cfs but i was apparently wrong.

it seems short of drilling into my teeth no one can agree on a decent way to dignose it. even drilling my teeth is not guarenteed and its these procedures that can, and possibly have created room for the infection to begin with

 

[Tunguska]

I don't know if we'll ever know for sure but I'm guessing that the rapid improvement with Rapamune for CFS/ME is more immune suppression related rather than anti-viral or mitochondrial, everything I've read about anti-virals says it takes months to make progress against a persistent infection.

I think rapid relief could be rather the combination of immune modulation together with the ability to prop up overall cellular metabolism (not necessarily mitochondrial alone although I think it should, I just cannot justify this very well). A lot of the most useful substances are so because they work on multiple pathways simultaneously so I start from this assumption, and then try to figure out which is the most significant.

I'm doubting rapamycin as a drug has any unique effect on viruses. Or that it needs any unique consideration as an "immunosuppressor" in this respect. It all goes back to:
http://forums.phoenixrising.me/inde...-encephalopathy-cfs.48446/page-36#post-823877 Any drug that modulates Akt/mTor in any direction must be considered immunomodulatory toward infections whether it's been formally identified as such or not, and the effect is not unique to the drug but rather to your viral profile, and you may not be be able to predict the effect reliably. Any long course of anything we've talked about for the last 3 months - just as with antivirals - should be accompanied by viral titer testing at some point, to prevent worsening of disease parameters that are not subjectively noticeable in time. As long as you take this into account then risk of experimentation is low.

What knackers describes from another drug could just as well as be bacterial infection which is not quite the same, and if the infection isn't measurable then that's a different risk although obviously the symptoms made it self-limiting, so...

 

[Jesse2233]

@Tunguska

What do you make of rapamycin effect on regulating B cells affected by lipopolysaccharides in graft verse host disease? Might this tie rapamycin's potenial effectiveness to De Meirleir's work on gram negative bacteria and lipopolysaccharide toxicity?

Sirolimus inhibits lipopolysaccharide-induced proliferation of B cells resistant to TAC and CSP [11,12].

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2563039/#!po=9.37500

 

[knackers323]

this appears to be someone who gets benefit from once monthly dose of rapamycin.

https://cfsremission.com/2017/05/14/success-from-two-readers-using-the-model/

 

[Jesse2233]

From @knackers323's link

“BTW – I’m working full time now!

After a few years of essentially being too weak to leave house or even blog, this is a huge breakthrough for me. I hope I can stay as high-functioning as I am now. Still a bit unsure which intervention pushed me over the edge of functional but very grateful for you and your site. Thank you Ken!

For instance, I likely would have resisted chronic antibiotic use if I hadn’t read your site. And I had given up on going to doctors (although now that I have a job again, I have an appointment with a new integrative doctor 5/22). Antibiotics are definitely the foundation of my recovery. If I had to estimate, I’d assign various treatments this rough spread of credit:

• 50% – Rotate daily Doxyciline or Kapsida weekdays + Mutaflor or Equilibrium weekends
• 30% – Once Monthly Rapamycin and/or LDN on Friday nights
• 20% – Armodafinil + Mt Dew on weekdays + weekend washout to prevent tolerance

Pretty simple model. Doxy kills bad bacteria. Kapsida also works as antimicrobial and seems to potentiate other antibiotics. Bursts of Equalibrium and Mutaflor definitely add baseline wellbeing and energy over antibiotics alone.

Rapamycin resets immune system whenever antibiotics stop working. Amazing to bounce back same day vs random downward tolerance spirals where everything stops working.

LDN serves same function as Rapamycin. It can additionally reset any stimulant tolerance. I try not to take high enough doses of stimulants to develop tolerance there too often so I mostly skip LDN unless I’m really in trouble. It’s definitely the ickiest drug in my mix and probably net bad for anyone long-term.

Armodafinil obviously extends willpower, mood, and vigilance. It’s a band-aid but even half doses are a really good bandaid. It takes me from simply well enough to sit up on the coach and not feel weak –> well-enough to work in an office with others all day.

 

[ErdemX]

this appears to be someone who gets benefit from once monthly dose of rapamycin.

https://cfsremission.com/2017/05/14/success-from-two-readers-using-the-model/

So looks like there are quite different protocols of this drug. Daily dosages such as 1 or 2 mg, or bigger dosages once in a week / 2-3 weeks or a month.

I think the result might be different for the same person.

 

[knackers323]

judging from the quote it sounds as if the person who posted it attributes rapamycins benefit to effects of the drug that are probably considered unconventional and largely unknown.

has anyone heard of these supposed effects from it before?

anyone know what a once per month dose would be?

 

[dreampop]

From @knackers323's link

Well I have a feeling it isn't the antibiotic since that's a pretty common treatment.... I took doxy for a year.

 

[Jesse2233]

Well I have a feeling it isn't the antibiotic since that's a pretty common treatment.... I took doxy for a year.

Perhaps it's the combination. He strangely also mentions Mountain Dew (the soft drink)

 

[dreampop]

Perhaps it's the combination. He strangely also mentions Mountain Dew (the soft drink)

Patient: Doc, I have CFS, what do I do??!

Doctor: Do the Dew

 

[XenForo]

Coming back here a week later to say I'm still doing better than ever. Still have CFS, but greatly reduced symptoms still. I need to stop working hard for 12 hours straight; that causes a crash the following day. If anything would cause me a crash, it would be that, and it apparently still does. I guess I needed to learn my new limits.

Oh and I'm still off the Rapamune, but still part of me really wants it back.

 

[knackers323]

@XenForo what dosing were you taking of the rapamune?