Dr. Avik Roy is the chief scientific officer at the Simmaron Research Institute, a non-profit organization dedicated to understanding ME/CFS and related diseases and to treating people with these diseases. Solve ME has long supported Dr. Roy’s work through multiple grants. These include a Ramsay award in 2022 and, most recently, a Catalyst award.
Dr. Roy’s team recently published exciting results in the Journal of Translational Medicine from a clinical trial to test whether rapamycin is safe for treating people with ME/CFS and for reducing cardinal symptoms of the disease. In some people with ME/CFS, muscle cells have trouble with autophagy (the process by which cells clean out debris), and this dysfunction can cause chronic muscle fatigue. Earlier, the team showed how the FDA-approved drug rapamycin restored autophagy and reduced fatigue-related symptoms in mice.
Here, the team took major steps in showing that rapamycin is safe and effective for humans, too. High doses of rapamycin can cause serious adverse effects, like metabolic problems (anemia and insulin resistance) and susceptibility to infections. But in this study, the researchers gave a low dose to participants; and participants had no serious adverse effects and only mild adverse effects (like gastrointestinal symptoms and headaches) that went away with time. In fact, among the participants who left the trial before finishing, many did so because they couldn’t afford treatments or tests, not because they had serious adverse effects. The team also showed how rapamycin treatment improved autophagy, physical function, sleep, and quality of life and reduced post-exertional malaise, fatigue, and orthostatic intolerance. Almost three in four participants experienced less post-exertional malaise, fatigue, and orthostatic intolerance during the 90-day treatment. The participants who improved the most were the ones for whom rapamycin restored autophagy functioning the most, supporting the idea that problems with autophagy were driving these ME/CFS symptoms.
A key result from this trial was that treatment responses of people whose ME/CFS disease followed viral infections were better than responses of people whose disease did not follow viral infections. This suggests that rapamycin is especially effective for people with infection-induced ME/CFS or for people with herpesviruses reactivation–associated ME/CFS. Another important result was establishing molecular assays to measure two blood-based biomarkers for finding which participants had the most problems with autophagy and, thus, who would probably benefit from rapamycin treatment.
Overall, this study strongly links dysfunctional autophagy with fatigue-associated symptoms of ME/CFS and supports using rapamycin to treat people with autophagy-driven ME/CFS symptoms. Furthermore, this work established valuable molecular tests and biomarkers to find which people would respond best to this treatment. But the team noted several important issues to address next. First, because the team had limited funds and enrolled few participants (86 people), they did not treat some people with placebo. Second, the team measured improvements by using subjective questionnaires, not by using objective clinical tests. Third, the team was forced to use different preparations of rapamycin, and some preparations may have been better than others at improving patients’ autophagy.
Supported by more funds from Solve, Simmaron has already launched a larger clinical trial to address these and other issues. In this new trial, the team will enroll more patients (allowing comparison of rapamycin and placebo treatments); gather objective clinical data by distributing wearable devices and collecting biospecimens; and give participants a more standardized preparation of rapamycin, at no charge.
“This funding from Solve M.E. will help us continue enrollment in our ongoing expanded phase in collaboration with AgelessRx and cover the cost of study drug and safety labs in this decentralized study,“ noted Simmaron CEO Dr. C. Gunnar Gottschalk. “Our goal is to develop a predictive test to identify which patients are more likely to benefit from rapamycin or other mTOR-targeted therapies.”
Solve recently hosted a webinar with panelists from the Simmaron Research team who discussed early results from this study and their unique goal to identify a biomarker to predict who is likely to respond to this treatment. Watch the webinar here.