Trial Report Low Dose Rapamycin Alleviates Clinical Symptoms of Fatigue and PEM in ME/CFS Patients via Improvement of Autophagy, 2025, Ruan et al

[V.R.T.]

The wasf3 paper is probably the best evidence we have but it needs to be followed up.

Anyone got any word on whats going on there? Last I heard Hwang et al were moving ahead with a small drug trial...

 

[Covidivici]

Disclaimer, this is 100% anecdotal:

Interestingly, rapamycin initially restored my energy and mental sharpness to the point where after two full weeks of feeling great, I risked a HIIT workout (spoiler: that was not smart. It led to a PEM crash). The crash lasted two weeks. Another three weeks went by with me resuming some function (not quite as much as before the crash) until, out of literally nowhere (I live in an airtight bubble), I came down with flu-like symptoms, then tested positive for COVID.

That was a major WTF moment.

Other than feeding/hanging out with my neighbours' cat during their trip abroad (with N95 on for the first four days, then without which I assume was my mistake — that cat is a kisser) I can't see how I could have caught it. I never leave home without a fit-tested N95 and even then, it's just to walk to the pharmacy or grocery store. No one else in my household ever tested positive. My spouse was livid: They do everything to keep me safe and here I went and got sick again on my own.

I was so flabbergasted that I actually wondered if rapamycin might not have led to either reactivation of the virus (following the viral persistence theory) or for a mutated version of it to break through. Neither of which I've ever heard of happening to anyone.

So yeah, it was probably the f%@ing cat. Consequently, my baseline ended up halved. I went from functional-but-cautious-not-to-trigger-PEM to basically bed bound. End of anecdote.

Edit: not sure what mitochondrial issues Dr Younger is referring to as there is no clear evidence for a specific mitochondrial problem yet.

I was under the impression that Rob Wüst was onto something:

"Biopsies of Long COVID patients vs controls before they exercised showed little difference. But as soon as they'd done mild exercise, the control group's mitochondria got more efficient whereas those with Long COVID (now suffering from PEM) got worse."

Relevant thread:

Preprint Thread 'Skeletal muscle properties in long COVID and ME/CFS differ from those induced by bed rest, 2025, Charlton, Wust et al'

May 6, 2025

Abstract:
Patients with long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) suffer from a reduced exercise capacity, skeletal muscle abnormalities and post-exertional malaise (PEM), where symptoms worsen with cognitive or physical exertion. PEM often results in avoidance of physical activity, resulting in a lower aerobic fitness, which may contribute to skeletal muscle abnormalities.

Here, we compared whole-body exercise responses and skeletal muscle adaptations after strict 60-day bed rest in healthy people with those in patients with long COVID and ME/CFS, and...

• Nightsong
• bed rest deconditioning long covid me/cfs muscle rob wust
• Replies: 56
• Forum: ME/CFS research

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[wingate]

rapamycin is a f***ing nasty drug

Could you elaborate on this? What makes it so bad?

 

[Utsikt]

Could you elaborate on this? What makes it so bad?

For those forum members who don't know. mTOR is basically the central agent that controls cell metabolism (it has two functional complexes mTORC1 and mTORC2) it has its fingers in every pie that you can imagine. Because of this and because of cancer I would not be surprised if it is the single most researched protein kinase in history (which is an advantage, we know how it fits into a lot of cell biology in detail)