mTor Inhibitor Rapamune Helps 5 ME/CFS Patients in Dallas

[Joe Smoe]

I needed to get some serious stuff done, and went back on Rapamune June 12th, so it's been 10 days now. I'm back to being productive again. I reviewed and revised some very confusing paperwork. And I did some serious demolition work, some of which involved a jackhammer. Man it feels great to feel "normal" again. I remember having this much energy when I was a little kid. However, the jackhammer was not really a good idea, as I've been a little too tired today to be as productive.

... taking Rapamycin twice a week cuz it's half life is approx 3 days. 3mg twice a week is what I'm going to start. I've been taking 5mg once a week for a month and had major improvements. I too have had moments of "normal." @XenForo I think we're onto something here.

 

[nandixon]

After 4-6 weeks on Rapamycin 5 mg once a week, I have seen some dramatic improvements in activity level.

On another thread you mentioned that you have “highly elevated Autoantibodies.” Which autoantibodies were found elevated?

 

[XenForo]

More on everolimus... I've not seen everolimus discussed here either

Gosh, I'm so curious about everolimus. Looks safer. I wonder if it would have a similar effect to sirolimus. I can't wait for someone to try it and post results!

 

[msf]

Just thought I would plug my blog (the 2nd one I posted in this thread) here, as it mentions posible positive consequences of mTOR inhibition in ME patients. http://forums.phoenixrising.me/index.php?threads/my-current-understanding-of-me.51319/

 

[msf]

And here is a study that seems to back up what I was suggesting, at least in normal people: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4302759/

 

[XenForo]

Here's an interesting comment from Cort at Health Rising, posted in the comments section, here: https://www.healthrising.org/blog/2017/03/08/davis-strategic-approach-chronic-fatigue-syndrome/

Cort Johnson on March 8, 2017 at 9:01 pm
I actually had something about the mTOR subset in the original blog but took it out. As I remember [Ron] Davis has found two patients with mutations in the mTOR gene involved in energy production, cellular stress and other factors. The reason I didn’t put in is that my assumption is that that mutation is quite rare in ME/CFS patients. I remember Ron saying that he had found mutations in a couple of patients in the severely ill study. While those mutations might very well be causing those patients problems they had no impact on the other patients.

So I think he’s referring to a very small subset and would probably be really interested in yours and other experiences. Davis’s serum findings suggest that a protein such as an autoantibody may be whacking the energy production system in ME/CFS. If it is an autoantibody then an immunosuppressive agent could be very helpful...

Maybe there is in fact an mTOR subset of us that respond to mTOR downregulatoring drugs?

 

[XenForo]

According to the below paper "mTOR complexes in neurodevelopmental and neuropsychiatric disorders" in Nature Neuroscience, Torin (Sertraline / Zoloft) is a more potent mTORC1 inhibitor than Rapamycin. I wonder how well Zoloft would also work for us, vs Rapamune?
https://cyber.sci-hub.cc/MTAuMTAzOC9ubi4zNTQ2/costamattioli2013.pdf
EDIT: here's another paper, "Updates of mTOR inhibitors" from Anti-Cancer Agents in Medicinal Chemistry: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2980558/

 

[Tunguska]

According to the below paper "mTOR complexes in neurodevelopmental and neuropsychiatric disorders" in Nature Neuroscience, Torin (Sertraline / Zoloft) is a more potent mTORC1 inhibitor than Rapamycin. I wonder how well Zoloft would also work for us, vs Rapamune?
https://cyber.sci-hub.cc/MTAuMTAzOC9ubi4zNTQ2/costamattioli2013.pdf
EDIT: here's another paper, "Updates of mTOR inhibitors" from Anti-Cancer Agents in Medicinal Chemistry: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2980558/

Are you sure Torin is the same as Sertraline? I didn't picture Sertraline being an inhibitor of mTor e.g. https://www.ncbi.nlm.nih.gov/pubmed/24901414

In any case my theory hasn't changed that much in that the Akt-sustaining property of Rapamycin should be significant i.e. allow it to exert its immune cell mTor inhibition effects without too negatively affecting regular (muscle) cells in the short term, so I'd look for that property in the other inhibitors versus full Akt/mTor repression.

I've had increased interest in trying Rapamycin myself but nobody will ship it to my nanny-state country (think I'm talking about the UK? think again!).

 

[Tunguska]

Hmmm. I feel like the Rapamune works when I take it along with morning ghee (clarified butter) and doesn't work when I don't. I'm not sure, and have no idea why that would make a difference. Although I thought I remembered reading that rapamycin effects cholesterol levels.

This is a great tip actually. Since the intestinal absorption of Rap varies greatly and fat does impact absorption of other substances, even if I wouldn't have immediately thought of combining Rap with fat. Esp. considering the cost, maximizing absorption should be a priority.

 

[Tunguska]

Hmm, could be something to Sertraline. It can inhibit mTor in some cells apparently: http://cancerres.aacrjournals.org/content/70/8/3199.long

The inhibitory effect of sertraline on mTOR activity was observed as early as 1 hour at 10 μmol/L and continued through 16 hours of treatment (Fig. 2B). The serine/threonine protein kinase Akt is a major regulator of mTOR, and we noted that phospho-Akt status was unchanged upon sertraline treatment in MCF-7 cells (Fig. 2B). We did not detect changes in levels of caspase-3–dependent poly(ADP-ribose) polymerase cleavage in MCF-7 cells treated with 20 μmol/L sertraline for 24 hours (Supplementary Fig. S2), indicating the observed sertraline-mediated mTOR inhibition is not an indirect consequence of cell death. We also observed inhibition of mTOR activity in HeLa cells upon sertraline treatment, thus excluding that the effects documented here are cell line specific (data not shown).

The unchanged Akt status makes it interesting I suppose, but don't know how applicable this is.
[Sorry if I'm behind on this]

 

[XenForo]

... the Akt-sustaining property of Rapamycin should be significant i.e. allow it to exert its immune cell mTor inhibition effects without too negatively affecting regular (muscle) cells in the short term...

According to a paper in the journal Cancer Cell, The effect of rapamycin on Akt may vary with drug dose, with lower doses leading to greater Akt activation and higher doses leading to less Akt activity.
https://moscow.sci-hub.cc/ed52baf1b03c24b982247345fbc60940/phung2006.pdf

I don't have enough of a grasp of the material to know if this means taking a larger dose of rapamycin can lead to less Akt activity than taking no rapamycin at all, or just that taking a lower rapamycin dosage allows more Akt than taking a larger dose of rapamycin. And I don't know how to convert ng/ml to mg dosage of Rapamune. But I thought this looked potentially interesting.

 

[Tunguska]

According to a paper in the journal Cancer Cell, The effect of rapamycin on Akt may vary with drug dose, with lower doses leading to greater Akt activation and higher doses leading to less Akt activity.
https://moscow.sci-hub.cc/ed52baf1b03c24b982247345fbc60940/phung2006.pdf

I don't have enough of a grasp of the material to know if this means taking a larger dose of rapamycin can lead to less Akt activity than taking no rapamycin at all, or just that taking a lower rapamycin dosage allows more Akt than taking a larger dose of rapamycin. And I don't know how to convert ng/ml to mg dosage of Rapamune. But I thought this looked potentially interesting.

This would be good information, can't read it today. The mechanism that was described for the mTorC2/Akt inhibition after long-term treatment in the other papers didn't strike me as something that would apply to short-term large doses, so maybe this would help my understanding. But the usual disclaimer about these being cancer cells applies. For the dosage maybe try Hip's formula http://forums.phoenixrising.me/inde...cfs-and-fibromyalgia.38739/page-3#post-619887

 

[Gingergrrl]

Not sure about him but I've been found to have 4 of the 7 Cell Trend AABs. Alpha adrenergic and muscarinic acetylcholine receptor autoantibodies.

I am drastically behind in this thread but wanted to ask all of the experts on this med if it usually works best in patients with proven autoantibodies (vs. another sub-type of patients)?

I did the full Cell Trend panel 2x and was positive for seven of the nine autoantibodies both times (plus a bunch of other autoantibodies not from Cell Trend). I have not researched this med at all but have found this thread very interesting (even though I have not read or understood it all).

 

[dreampop]

I'm six weeks into Sirolimus, 3mg twice a week, and I have had significant improvements. This coming after probably 150 plus unsuccessful interventions.


Not sure about him but I've been found to have 4 of the 7 Cell Trend AABs. Alpha adrenergic and muscarinic acetylcholine receptor autoantibodies.

Can you describe your illness before treatment, if it was relapsing/remitting or constant, including onset, and the percent changes to symptoms on Rapamycin? Are you concerned about the cancer risk taking it long term?

Glad your feeling better - this drug definitely seems to be working in quite a few people, but carries some serious risks.

edit: also, what prompted you to try this drug? this thread? or was it rxed by a doctor?

 

[Jesse2233]

Montoya is now using Rapamune / sirolimus https://www.reddit.com/r/cfs/comments/6lrf1o/comment/djxtzzs?st=J52OJQ02&sh=6b122561

 

[XenForo]

Montoya is now using Rapamune / sirolimus https://www.reddit.com/r/cfs/comments/6lrf1o/comment/djxtzzs?st=J52OJQ02&sh=6b122561

Oh that's GREAT news (potentially). When I had my yearly in person appointment recently, Montoya's PA was familiar with Sirolimus, but didn't offer it to me as an option. They offered Sulfazalazine, then Curamin instead, as they are less risky. Those other drugs didn't do anything for me though.

 

[Steve4Andrea]

That is very interesting, do we know for sure that it is Montoya approved and not just a rogue PA.

I ask because I have had concerns about the yin/yang action of an anti viral used with an immune suppressor, we stopped using Rapamune when we started Arbidol because of that concern. If the two drugs will play well together then the Rapamune can be used to moderate the IRIS response that comes with anti viral's for so many patients.

I am not convinced of the risk for Rapamune, all of the studies I found involved prior use of other immune suppressors and simultaneous use of Prednisone. The dosages we are looking at are a lot lower than the anti rejection studies use and I haven't yet found a study of low dosage on non-transplant patients.

 

[Jesse2233]

That is very interesting, do we know for sure that it is Montoya approved and not just a rogue PA.

Not sure, but I would think any drug prescribed by Stanford would have Montoya's blessing

Just got an email from Marcia (the original person to try Rapamune). Shared with her permission:

Operating now at about 85% most of the time. Still pacing but tolerating much much more activity, physical and cognitive [...]

I reduced my Sirolimus dosage to 2mg three times per week with no decline in function or increase in symptoms. Trying to determine the optimum dose to achieve symptom relief, as I know the side effects can be troublesome. Frankly I am hoping for a solid remittance.

I also recently stopped LDN to test if there would be any change in symptoms, and had none. And actually I am sleeping better without it. I am not clear on why I would not experience a decline after stopping LDN because it was the only thing that had previously helped. Have only been off the LDN for about 10 days so we shall see.

 

[nandixon]

Just got an email from Marcia (the original person to try Rapamune). Shared with her permission:

Do you know if Marcia has had any autoantibody testing done?

Also, when she mentions that she's “Trying to determine the optimum dose to achieve symptom relief, as I know the side effects can be troublesome,” do you know if she is currently experiencing side effects, or is she trying to prevent them from arising in the first place?

 

[Jesse2233]

Do you know if Marcia has had any autoantibody testing done?

Also, when she mentions that she's “Trying to determine the optimum dose to achieve symptom relief, as I know the side effects can be troublesome,” do you know if she is currently experiencing side effects, or is she trying to prevent them from arising in the first place?

Not sure but I can ask