The Simmaron Research Foundation

Creativity and productivity have been the hallmarks of Simmaron’s small research team.

Clinical trials – once a rarity for chronic fatigue syndrome (ME/CFS) – suddenly seem to be popping up all around the place. The Open Medicine Foundation just announced its first two-fer (two drugs tested together) clinical trial, Solve M.E. has funded at least 4 small trials over the past couple of years, and now we have Simmaron’s first clinical trial.


  • The Simmaron Research Foundation’s research team of Avik Roy and Gunnar Gottschalk has been making waves with their work on not one but three mouse models for ME/CFS, and their work suggesting that the cellular cleanup process called autophagy has gone awry.
  • This time, they and the Simmaron Research Foundation have really outdone themselves, though:  they’re about to begin a 100-person trial of Rapamycin (Rapamune) – a possible mitochondrial enhancer.
  • The trial’s origin has roots in the research program’s work in mouse and human studies, which found high levels of a compound called ATG 13 which suggested that problems with autophagy existed.
  • Problems with autophagy could interfere with many cellular processes, the most significant of which, for our purposes, may be the inhibition of mitochondrial activity and the production of free radicals.
  • Studies showing that Rapamycin has been able to extend the lifespan of several organisms have sparked interest in the longevity-enhancing potential of the drug. The drug inhibits the mTORC1 pathway, which in turn inactivates autophagy.
  • Last year, Health Rising published a Rapamycin recovery story involving a physician who’d been ill for ten years.
  • Simmaron’s non-placebo-controlled pilot trial will include 100 patients under the care of Drs. Kaufman, Chheda, Peterson, and one other doctor to be named soon. The trial, which is expected to last at least 18 months, is designed to provide data needed to get funding for a more rigorous placebo-controlled trial.

This one was a real shocker, but I’m not sure why. After all, I’ve gotten pretty used to being shocked by the small Simmaron Research team (Avik Roy Ph.D. and Gunnar Gottschalk Ph.D.). First, back in the beginning of the coronavirus pandemic when testing supplies were lacking, they developed a novel way to use urogenital swabs to test for the coronavirus.

Next, they showed, in two papers, that the coronavirus doesn’t actually need to enter the cell to damage it – all it has to do is attach itself to the ACE-2 receptor. That’s a very interesting finding given the apparent ACE-2 dysregulation also found in ME/CFS and POTS which could help explain the reduced blood flows, low blood volume, poor mitochondrial functioning, and others in that disease. They also developed an ACE-2 receptor modulator called the ACIS KEPTIDE and received a patent for it.

They’ve been moving towards fulfilling an immense need in this disease by working on not one or two but three ME/CFS mouse models (for PEM, POTS, and brain fog). They won a Ramsay Award in 2022 and received a rare NIH grant in 2023.

Mouse and Human Studies Lead to Rapamycin Trial

Still, I never anticipated the team would be able to pull off a 100-person clinical trial of one of the most intriguing drugs out there – rapamycin – a possible mitochondrial enhancer.

The rapamycin trial has its roots in Simmaron’s mouse and human studies. Mice were given two compounds, one of which activated the mTORC1 pathway and one that inhibited autophagy – a cellular cleanup process that’s crucial to mitochondrial functioning.

The mice responded by exhibiting high levels of ATG13 – a marker suggesting that problems with autophagy were present – and by looking like they had ME/CFS. Interestingly, the female mice were much more likely to become ill, quickly became fatigued when asked to exercise, and their grip strength declined.

Moving from the mice to humans, the Simmaron team found the same evidence of a breakdown in autophagy (high levels of ATG13) in ME/CFS patients’ serum. When autophagy breaks down, it can impair oxygen consumption and mitochondrial activity, affect immune functioning, turn cells into pro-inflammatory generators, and lead to clumps of proteins that can damage all sorts of cellular processes.

Applying the serum from ME/CFS patients to cultured microglial cells caused the microglial cells to erupt into activity and spew out free radicals and produce iNOS (nitric oxide) – an inflammatory and neurodegenerative form of nitric oxide. Meanwhile, the serum from the healthy controls had no effect on microglial activity.

Next, they used an antibody to neutralize the ATG13 in the serum, and tested it again. When the ATG13-free serum failed to turn on the microglia to the same extent, they concluded that ATG13 was the culprit in the ME/CFS patients’ serum.

Cleaning Crisis? Defective Mitochondrial Cleanup In ME/CFS May Be Impairing Energy Production

That finding set the stage for the trial of an mTORC1 inhibitor called rapamycin in 100 people with ME/CFS. Interestingly, just last year, Health Rising presented the story of a physician who has recovered from ME/CFS using rapamycin (Rapamune).

Rapamycin (Rapamune, Sirolimus)

Rapamycin mTORCI

A model of rapamycin latching onto mTORC1 and preventing it from activating.

Touted by some to be a longevity drug, rapamycin (Rapamune) inhibits inflammation by preventing T and B cells from activating.

Like so many other drugs, it has a fascinating backstory. Produced by a bacterium called Streptomyces hygroscopicus, rapamaycin was first isolated back in 1972 from samples gathered on Easter Island of all places. (Its name came from the native name for the island, Rapa Nui, where it was found.) Initially developed as an antifungal agent, researchers soon became more interested in its ability to inactivate the mTORC1 pathway.

The mTORC1 pathway functions as a kind of energy/oxidative stress sensor and is regulated by a number of factors including Rapamycin. The pathway does a number of things, but its main interest for ME/CFS is that it inactivates autophagy – the process through which cells cleanse themselves of old and damaged compounds which would otherwise interfere with mitochondrial production and cellular functioning.

Since declines in autophagy have been associated with aging, Rapamycin’s ability to tamp down the mTORC1 pathway and restore autophagy has made it of much interest to the longevity community.


The mTORC1 complex

Interest in Rapamycin’s longevity properties began in the early 2000s when it was shown to slow aging in worms, yeast, flies, and ultimately mice. Interestingly, Rapamycin appears to both inhibit (reduced TNF/IL-6) and stimulate (increased IL-12 / decreased IL-10) the immune system. The IL-10 inhibition might be helpful in ME/CFS, as a recent study suggested that increased levels of IL-10 may be hampering the acute immune response – allowing bacterial toxins to flourish.

Health Rising’s Rapamycin Recovery Story

Prior to ME/CFS, the doctor’s favorite activity was mountain climbing! Just a year earlier, the 69-year-old had climbed to the top of an 18,000-foot extinct volcano in Chile. He was, as he said, “living life to the fullest.”

An upper respiratory infection, though, knocked him down and seemingly out for good. After working all his life in an intellectually challenging career, he found he could only concentrate for two hours at a time, could not handle household chores and, at times, couldn’t walk a block. His social life was nonexistent. This went on for ten years.

A Rapamycin Resurgence: An MD Moves the Needle on his ME/CFS

His literature search led him to Rapamycin and he began an N=1 trial. Rapamycin’s inhibition of mTORC1 activity, its potential as a longevity drug, and its potential to reduce lactate production, increase ATP levels, improve cognition, and induce autophagy all recommended the drug.

He’d tried numerous treatments, but upon taking low-dose Rapamycin (6 mg once weekly), he noticed an improvement in three weeks, and by six weeks he was in full remission.

The Rapamycin Trial

Four doctors will assess rapamycin's effectiveness in ME/CFS.

Four doctors will assess Rapamycin’s effectiveness in ME/CFS.

A hundred people under the care of David Kaufman MD and Bela Chedda MD at the Center for Complex Diseases, and Daniel Peterson MD at Sierra Internal Medicine (and one more doctor to be named) will be given the drug.

The dosage will be determined by each doctor.  Autophagy markers will be taken before the trial, then at the maximum dose, and 30 days at each time point thereafter.

The goal of this non-placebo-controlled pilot trial is to gather enough data to get funding for a larger, more rigorous trial. The trial will assess symptoms and autophagy markers, and probably last from 18 months to 2 years.

Rapamycin has been around a long time and is known to be a safe, affordable drug – meaning should the pilot trial succeed, physicians will likely be willing to give it a try.

Simmaron asks that if you are on Rapamycin and have ME/CFS, or you have been told by your doctor that they plan to start you on Rapamycin, please email them at connect@simmaron.com.

Kudos to the Simmaron Research Foundation for investigating such an intriguing drug!

Enjoy Learning about the Latest Clinical Trials?

Please Support Health Rising and Keep the Information Flowing





Like the blog you're reading? Don't miss another one.

Get the most in-depth information available on the latest ME/CFS and FM treatment and research findings by registering for Health Rising's free  ME/CFS and Fibromyalgia blog here.

Stay on Top of the News!

Subscribe To Health Rising’s Free Information on Chronic Fatigue Syndrome (ME/CFS), Fibromyalgia (FM), Long COVID and Related Diseases.

Thank you for signing up!

Pin It on Pinterest

Share This