Rapamune / Rapamycin/ mTOR

Discovered on Easter Island, rapamycin has a unique history and impacts the mTOR pathways in our bodies.

mTOR is like a general contractor in sensing nutrients and regulating homeostasis in all cells.

The chat touches on ME-related things like how mTOR senses ATP, keto diets, methionine, diabetes, longevity.

Fwiw, I've been taking Rapamune, an mTOR inhibitor, since November. Its doubled my capacity: I can now walk up 2 flights of stair in a row.

After hearing the Sabatini interview, I have reduced my daily 1mg to every other day.

STEM Talk podcast: https://itunes.apple.com/ca/podcast/stem-talk/id1091402153?mt=2

From the podcast:

...describes David Sabatini’s discovery of mTOR ...gives us a first-hand account of how his research into rapamycin in 1994 as a graduate student led him to the discovery of mTOR, which we now know is a critical regulator of cellular growth.

Our interview with David delves into his continuing research into mTOR, which has led to promising opportunities for the development of new treatments for debilitating diseases such as cancer, diabetes and neurological disorders. He also discusses mTOR’s role in healthspan and lifespan.

David is a molecular cell biologist who, according to Reuters News Service, is on the short list for a Nobel Prize. David is on the faculty at MIT and heads up the Sabatini Lab at the Whitehead Institute.

In today’s episode, we discuss:
Rapamycin, a macrolide antibiotic discovered in the soil of Easter Island David’s discovery of mTOR while a grad student at Johns Hopkins mTOR’s role as one of the major growth pathways in the body mTOR’s role as a nutrient sensor How mTOR inhibiton has become one of the hottest topics in longevity research mTOR’s role in diseases, especially its connection to cancer The role of RAG GTPases as key mTOR mediators Protein intake and downstream mTOR activation Research into ketogenic diets effect on longevity and healthspan Whether David would take rapamycin as a means to enhance his longevity And much, much more

 

My experience with Rapamycin. I started a few weeks back and would just like to share progress.

Background: I've been housebound with ME/CFS for the past 13 years (diagnosed 2002). My main symptoms: fatigue, brain fog and sore lymph nodes (groin, under arms, and occassionally spleen).
I am aiming to maintain the dose used for antiaging (5-6 mg taken weekly).

Week 1 on Rapamycin: Possible lessening of lymph node pain? No significant change in ME.

Week 2 : More definite lessening of lymph node pain. Pain returned as I came toward the day for my next dose. Possibly a little better generally.

Week 3. Very little lymph node pain. My capacity beginning to improve.

Week 4 and 5. No lymph node pain. And capacity increased. Still housebound but able to function longer. Also, it is usual for me to do 'mental/physical activity' before my usual morning routine because by the time I have had breakfast, dressed etc., I am exhausted again. Now I can do my morning routine and then sit down to some task. Haven't been able to do that for over a decade!!

Week 6. Busy week at home and lymph node pain and fatigue returned. No words for disappointment! You'll know. I will increase the dose by 1mg and see what happens. Can't go any higher than that, though I would love to.

Side effects: second day after I've taken the weekly dose, I get agitated. It passes but is a noticeable pattern.
Possible concerns: Before starting treatment my lymphocyte count was below the normal range, so will need to keep an eye on that.

 

Latest update on rapamycin/rapamune/sirolimus:

I increased the dose but the lymph node pain and fatigue flared up badly afterwards.
So, I am back to cold baths and using ice packs to calm down my immune system.
Very sadly, I think my experiment with rapamycin is at an end.

Possible reasons it worked initially and then stopped: a) it does exacerbate some autoimmune conditions and has some proinflammatory effects so perhaps it was triggering something in this way b) even anti-inflammatory effects make me feel ill* so perhaps this was the cause c) who knows???

*Any med or supplement that is proinflammatory makes me feel terrible straightaway, but anti-inflammatories also make me ill, it just takes longer to manifest and the effect is less pronounced than with proinflammatories. I had hoped as rapamycin is immune suppressant that I could bypass all of this, but from my browsing of the literature it seems rapamycin's effect on the body is more complicated than I hoped

 

Merged thread
https://www.healthrising.org/blog/2022/07/06/apamycin-resurgence-doctor-chronic-fatigue-syndrome/

n=1

 

The comments mentioned another thread about someone who benefited from it, but also a comment from someone who almost died from taking it.

I remember coming across a list of treatments PWME have tried, and how they rated them. The results didn't seem all that useful, at least for trying to figure out which ones were really worth trying.

 

There is the ME Association survey from 2010




https://www.meassociation.org.uk/wp-content/uploads/2010/09/2010-survey-report-lo-res10.pdf

 

Yup, not very useful, especially since it's anecdotal evidence. My guess is that if they'd asked people to try magic crystals or random treatments meant for disease unrelated to ME, they'd come up with fairly similar numbers.

 

Link is broken. Here is a working link: https://www.ihmc.us/stemtalk/episode-70/

 

https://twitter.com/user/status/1851558622859255961


This person (25M) went from being bedridden with severe #LongCovid and PEM for 2.5 years to playing basketball within a few weeks of starting Rapamycin! It cured his PEM. Apparently a Rapamycin clinical trial will also start in the US come January.

 

PolyBio news about the planned Rapamycin trial.
https://polybio.org/polybio-supports-helps-conceptualize-long-covid-rapamycin-clinical-trial/

 

Trial registration for Simmaron Research study: Rapamycin in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

They will be giving a max dose of 6 mg/week to people with ME/CFS (IOM criteria), comparing outcomes between those with "serological evidence of autophagy disruption" to those without.

Estimated enrollment: 100

Outcomes are SF-36 (primary, 1 year) and "change in mTOR activation panel and blood markers involved in autophagy function" (secondary, 1.5 years).

Estimated study completion: 2026-06-11

From SimmaronResearch.com:

The mentioned study (thread):
Elevated ATG13 in serum of patients with ME/CFS stimulates oxidative stress response in microglial cells via activation of receptor for advanced glycation end products (RAGE), 2022, Gottschalk et al

 

I don't see the PolyBio study on long COVID on ClinicalTrials.gov, but here are some tweets about it.

-------

https://twitter.com/user/status/1851632219812516135

Amy Proal:

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https://twitter.com/user/status/1851625941778198738

PolyBio:

 

Someone on Reddit in the ME/CFS trial said Simmaron just finished the study. Their doctor told them most of her patients didn't benefit from it. This person had pretty minor improvements in brain fog and fatigue. They didn't say if they know which group (evidence of authophagy disruption or not) they were in.

From another comment they made, referring to their doctor: "She said people that benefit from Rapamycin are few, but for the few, it usually helps a lot and fairly early on."

 

Some info on the immunostimulatory properties of rapamycin.

Sirolimus (rapamycin) on Wikipedia:

It cites the following paper (which is from a different year than Wikipedia says, not sure why). I added line breaks for easier reading.

Regulation of innate immune cell function by mTOR, 2018, Weichhart et al

There are several more paragraphs about immunostimulation after this one in the paper.

 

Old video of Ron Davis, mentions mTOR inhibitors. (Starts at 5:05)

https://www.youtube.com/watch?v=jXL2xzxCXBw

I don't see why a mutation in mTOR implies that inhibiting it will make you worse. Is his thinking that a mutation is probably making it work less effectively, so inhibiting it would be adding to the problem? Isn't it possible a mutation is making it do too much of some process, so turning it down would be helpful?

I've read probably 10-15 anecdotes of rapamycin use in ME/CFS. I don't recall anyone saying they've gotten significantly worse. Mostly no change, with a few that had improvements.

Also, anyone know off hand if mTOR genes have popped up in any studies?

 

I'll make a list of anecdotal reports of rapamycin use in ME/CFS or long COVID. I'm sure if I kept going through Reddit search results for "rapamycin" I'd find more, but I'm tired now.

Worsened

1. Phoenix Rising
2. Phoenix Rising (temporary symptoms after stopping: Phoenix Rising)
3. Phoenix Rising

No change in ME/CFS symptoms

1. r/covidlonghaulers
2. r/covidlonghaulers
3. r/cfs
4. r/cfs
5. r/cfs
6. r/cfs
7. r/cfs
8. r/cfs (same person: r/cfs)
9. r/cfs
10. r/cfs
11. r/cfs (same person: r/cfs)
12. r/cfs
13. r/Rapamycin (Caused mild depression while on it)
14. Phoenix Rising (slight improvement in exercise intolerance, slight worsening of short term memory, 2 weeks)
15. Phoenix Rising
16. Phoenix Rising
17. Phoenix Rising
18. Phoenix Rising

Temporary improvement

1. r/covidlonghaulers (Update: r/Rapamycin)
2. r/cfs
3. r/cfs
4. Phoenix Rising

Improvement (though some are only a few weeks after starting, so might have ended up in temporary improvement)

1. r/cfs
2. Health Rising (7 months)
3. Health Rising (search comments for "physical and cognitive functionality")
4. r/covidlonghaulers (update: r/covidlonghaulers) (9 months)
5. r/covidlonghaulers (update: r/covidlonghaulers) (Over 1 year, but I'm not sure if it helped fatigue or PEM for them. They say it helped "inflammation" and "healed the brain".)
6. r/cfs (updates: r/cfs, r/Rapamycin) (At least 4.5 months)
7. r/cfs (5 months)
8. r/cfs (Updates: r/cfs, r/covidlonghaulers) (Improved energy but worsened hyperadrenergic POTS and nonepileptic seizere frequency, so they stopped)
9. r/covidlonghaulers (At least 6 weeks)
10. r/covidlonghaulers (helped brain fog, but not PEM)
11. Phoenix Rising (4 weeks)
12. Phoenix Rising (Update: Phoenix Rising)
13. Phoenix Rising

Four more improvements that I didn't include, in the collage here. It's the Twitter screenshots. r/cfs

Edit: Added posts from Phoenix Rising

Edit 2: Added one to Worsened and two to No Change.

 

Unfortunately, I didn't respond to rapamycin. I took 5 mg/week for 4 weeks. It's been 3 weeks since my last dose.

I was planning to do 2 months, but I was worried it was making me worse. I was getting slightly worse but hard to say if rapamycin was the cause, as I've been declining for a while.

I got a canker sore a few days in for a very short time. I also had a pretty bad sore throat from around days 4-6, which then turned into a runny nose for a couple days. A milder sore throat the second week. And that's pretty much it for side effects.

 

'Simmaron has already found 130 age and gender-matched healthy controls over the past year, but they are not including a placebo arm in this trial because they’re seeking FDA approval for the drug in ME/CFS in another way.

They aim to develop a diagnostic panel using pATG13 and BECLIN-1 to predict who responds to Rapamycin. They’re using a “high-complexity lab” called Coppe Labs (Konstance Knox, PhD), which specializes in the development of FDA diagnostic panels.

(If I have it right, if the clinical trials go as hoped, people with high pATG13 (blocks the MTORC1 pathway, which upregulates autophagy) and low BECLIN-1 levels (indicating low autophagy) will probably fit this profile). Ultimately, general practitioners will be able to order these labs to determine which patients should try the drug.'

https://www.healthrising.org/blog/2025/02/01/simmarons-rapamycin-chronic-fatigue-fda-approval/

No placebo arm in their phase 2 sounds completely wrong headed to me! What are they playing at?