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

but it does give a ceiling to how large the effect might be.
Yeah, that's pretty clear, thanks @ME/CFS Skeptic. There's really nothing there beyond what you'd expect from a placebo, natural fluctuations, and more than half of your cohort (probably the cohort with the least improvement) dropping out.

I did like the ATG13 work. I haven't read this study and I'm hazy on the previous work now, but do people think there is a way that finding might still be worth investigating?
 
I did like the ATG13 work. I haven't read this study and I'm hazy on the previous work now, but do people think there is a way that finding might still be worth investigating?
Putrino's lab with funding from PolyBio is running another trial. I was really disappointed that Amy Proal/PolyBio are reposting success stories on X of people posting a good response to Rapamycin and no poor responses.
 
Would be interesting to see the results for the Sf-36 physical functioning scale but it seems they haven't plotted that one (although it was measured).
I seem to remember the oxaloacetate trial paper promoted one of the physical function scales in the text of the paper vs the other which had null results (hope I'm remembering right). Sure would be nice to see Sf-36 data. Some of the same clinicians took part in the oxaloacetate and rapamycin open label trials.
 
The paper states:

Importantly, discontinuation from the study was most commonly attributed tofinancial barriers as this pilot trial did not cover the cost of the study drug or safety laboratory tests. A secondary reason for discontinuation was a lack of perceived clinical benefit or a clinical decision toinitiate a different therapy that may or may not interact with the study protocol.
But as someone pointed out to me on Twitter, table 1 shows that 'no change in symptoms' (n = 17) was more common than 'financially unable' (n = 10). So lack of perceived benefit seems to be the primary, not a secondary reason for dropout?

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I also don't get that if the main problem is that the drug is really expensive, then why would you include 86 participants on the drug, and nobody on a placebo (which costs virtually nothing).
CostPlus charges $61.24 for 30 x 2mg tablets plus $5 shipping. A fraction of the cost of a doctors visit to Kaufman.

I suspect the labs were much more expensive, as quite a few of the tests they were ordering are only covered once per year only on Medicare insurance e.g. A1C, Lipid panel. So tests before taking drug for a baseline snapshot would be covered but some of the next tests you would be hit with a surprise large bill (often 20x what insurance would have paid if it covered payment).
 
Jarred Younger video 061 - Low dose rapamycin for ME/CFS

Main points
* It's a huge no-no to not count drop-outs in your statistics.
* This is a paper for researchers, not patients or clinicians.
* It should in no way change prescribing habits.

Younger says that a 72% response rate is unlikely because we know the ME/CFS label contains 3 different pathologies. Unless I have missed something major, or he has seen advance results I haven't, we don't know anything of the sort.
 
Younger says that a 72% response rate is unlikely because we know the ME/CFS label contains 3 different pathologies. Unless I have missed something major, or he has seen advance results I haven't, we don't know anything of the sort.
Unfortunately in my ME/CFS local groups he is getting a lot of play with this video as it is in an easily digestible format, and lots of people had hope in this treatment. It’s an odd statement to make while in the same breath critiquing evidence for other hypotheses and data.

Anyone know where he’s pulling this phenotyping from?
 
Unfortunately in my ME/CFS local groups he is getting a lot of play with this video as it is in an easily digestible format. It’s an odd statement to make while in the same breath critiquing evidence for other hypotheses and data.

Anyone know where he’s pulling this phenotyping from?

It's not the first time I've seen him make it either.
 
I also don't get that if the main problem is that the drug is really expensive, then why would you include 86 participants on the drug, and nobody on a placebo (which costs virtually nothing).
I think because they were doing this virtually from home and the drug was being shipped from Ageless RX. I don’t think they had a system worked out for sending placebo from Ageless RX.

For a while when signing up for ageless it would ask you if you were in the trial. I tried to get rapamycin through ageless but was denied due to age, under 40.
 
One of the comments about the video states they got much worse when taking Rapamycin and took a long time to get back to baseline. I commend that person for speaking out.

Every damn treatment that trends - mestinon, ldn, this, whatever - always seems to come with reports of worsening as well as improvement. At least we will have the data from the placebo controlled Rapamycin study and the lift ldn mestinon study in the next year or two.
 
Unfortunately in my ME/CFS local groups he is getting a lot of play with this video as it is in an easily digestible format, and lots of people had hope in this treatment. It’s an odd statement to make while in the same breath critiquing evidence for other hypotheses and data.

Anyone know where he’s pulling this phenotyping from?
Dr Younger replied when I asked him about the 3 different patholgies.
Dr. Younger on YouTube comment said:
I will put this topic in my list of videos to make and will probably get it out in the next month. My quick description is: 1) microglia activation and central inflammation, 2) abnormal systemic immune system involving problematic T-cell activity, 3) mitochondrial problems and oxygen delivery issues to the brain. The story requires fitting several papers together right now. More soon! - Jarred Younger
 
 
rapamycin is a f***ing nasty drug so seeing anecdotes of people losing baseline and reading here that drop-outs were excluded from the results is worrisome given that people are going to see this study on twitter and ask their doctor for a prescription

Need double blinded rct urgently to clear this up because the genie is out of the bottle

Edit: not sure what mitochondrial issues Dr Younger is referring to as there is no clear evidence for a specific mitochondrial problem yet. The collective findings are the usual ME/CFS hodgepodge of “a bunch of people kept looking here and found various inconsistent things because this is where they all looked for things”. Myself of yore included. There is nothing clear or replicated. The wasf3 paper is probably the best evidence we have but it needs to be followed up. The more we throw the M word around without specific grounding the more power we give to predators peddling magic supplements for "energy".

One of the most often cited & discussed respirometry studies used mixed PBMC without characterising or sorting the populations, and some immune cell populations do many times more oxidative metabolism than others. Some almost don't at all. Small shifts can throw out the mean by several fold. This absolute pillar of these ideas is, sadly, almost meaningless.
 
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I did like the ATG13 work. I haven't read this study and I'm hazy on the previous work now, but do people think there is a way that finding might still be worth investigating?
In as many uncountable ways as any number of metabolic disturbances if present may interact with processes that we believe may drive the illness. These particular pathways affect pretty much all of the cell. It has to be framed within a specific, start-to-finish signalling process to be evaluated in specific terms.
It’s not that bad
It turns off the most central and interconnected protein kinase complex in mammalian biology
 
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