Weekly Rapamycin Shows Promise in Improving Symptoms of ME/CFS in Early Clinical Trial

Early results from a phase 1 clinical trial suggest that weekly administration of rapamycin may significantly improve patient-reported outcome measures (PROMs) in individuals living with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). The findings were presented by Stephanie L. Grach, MD, MS, assistant professor of medicine at Mayo Clinic, during the 2025 American College of Physicians (ACP) Internal Medicine Meeting, held April 3–5 in New Orleans, Louisiana.

ME/CFS is a complex, debilitating condition characterized by profound fatigue, post-exertional malaise (PEM), sleep disturbances, autonomic dysfunction, and a constellation of other symptoms. Current treatment options remain limited, prompting increased interest in therapies targeting underlying biological mechanisms.

“ME/CFS is a devastating infection-associated multisystem illness,” Grach and colleagues stated in their presentation. “Rapamycin has emerged as a candidate therapy due to its potential to modulate systemic inflammation and promote autophagy via mTOR inhibition.”

Study Overview

The data presented were drawn from the first 40 participants in the trial who had completed three months of follow-up. Participants received a starting dose of 0.5 or 1 mg of rapamycin weekly, which was gradually increased to a maximum of 6 mg per week or as tolerated. Throughout the study, participants completed several validated PROMs at baseline and monthly intervals:

• Bell Activity Scale (BAS)
• Multidimensional Fatigue Inventory (MFI)
• RAND SF-36 Health Survey
• Symptom Severity Scale version 2.2 (SSS), which assessed fatigue, sleep, PEM, and orthostatic intolerance

Routine safety labs were also conducted at each visit to monitor for adverse effects.

Key Findings

By the three-month mark, participants showed statistically significant improvements across multiple PROMs:

• Bell Activity Scale (BAS): Improved from 34.84 (SD 3.13) to 42.26 (SD 3.87); P < .001
• SSS Sleep Scores: Improved from 7.35 (SD 0.38) to 5.03 (SD 0.58); P < .001
• SSS PEM Scores: Improved from 7.05 (SD 0.39) to 3.77 (SD 0.56); P < .001
• SSS Orthostatic Intolerance (OI): Improved from 5.33 (SD 0.46) to 3.50 (SD 0.50); P < .001
• MFI Aggregate Scores: Decreased from 79.63 (SD 1.43) to 72.26 (SD 2.28); P < .001

These findings suggest a potential therapeutic benefit of rapamycin in addressing core symptoms of ME/CFS. Subgroup analyses and more detailed data are expected to be released in future publications.

Participant Profile

The cohort had a mean age of 47.43 years (range: 24.80–76.38), with 32% male and 68% female participants. The average disease duration was 16.45 years, and the majority (92%) identified as non-Hispanic White. The mean BMI was 26.64.

Scientific Rationale

Rapamycin, a well-known mTOR inhibitor, has gained attention in aging and chronic disease research for its anti-inflammatory and autophagy-promoting properties. Preclinical studies conducted by members of this research team have indicated that impaired autophagy—specifically involving the release of ATG13 into serum—could represent a pathological mechanism in ME/CFS.

“In line with suspected abnormalities of mTOR inhibition, the results of our study support the potential use of rapamycin in ME/CFS,” Grach and colleagues concluded.