Gile, Brooke, Bulbule, Sarojini, Toriola, Mubaraq A et al. · Journal of translational medicine · 2026 · DOI
A pilot study observed that people with ME/CFS who received low-dose rapamycin reported improvements in fatigue symptoms over 90 days, and blood tests showed changes in purine metabolism and mitochondrial energy markers. However, this was a small observational study without a placebo control group, so it does not yet establish whether rapamycin actually causes these improvements or whether the observed biochemical changes are responsible for symptom relief.
ME/CFS lacks proven disease-modifying treatments. This pilot work proposes a mechanistic hypothesis linking purine metabolism, mitochondrial dysfunction, and immune activation—three areas of active ME/CFS research. The preliminary identification of a specific metabolic pathway amenable to modulation may guide larger, controlled trials.
This observational study does not establish causation between purine metabolism changes and symptom improvement, does not confirm rapamycin's efficacy in ME/CFS (no placebo group and no untreated controls), does not prove that microglial inflammatory changes drive fatigue, and does not generalise beyond the responder cohort studied. The molecular findings are acknowledged by the authors as potentially biased toward those who improved clinically.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
The first block is for the primary paper and is the citation you should use in research work. The atlas-snapshot line only applies if you are specifically referring to this atlas’s reading of the paper on the date shown.
Primary citation
Gile, Brooke, Bulbule, Sarojini, Toriola, Mubaraq A, Ruan, Brian T, Marium, Shabnam, Benko, Anna, et al. (2026). Association of rapamycin treatment with the modulation of purine metabolism, reduced microglial inflammatory responses, improved mitochondrial energy metabolism, and alleviation of fatigue symptoms in ME/CFS subjects: pilot findings from phase-II observational study.. Journal of translational medicine. https://doi.org/10.1186/s12967-026-08575-3
BibTeX
@article{mecfsatlas-gile-2026-association-rapamycin,
author = {Gile, Brooke and Bulbule, Sarojini and Toriola, Mubaraq A and Ruan, Brian T and Marium, Shabnam and Benko, Anna and Grach, Stephanie and Mueller, Michael and Bateman, Lucinda and Bell, Jennifer and Yellman, Brayden and Berner, Jon and Chheda, Bela and Kaufman, David and Gottschalk, Gunnar and Roy, Avik},
title = {Association of rapamycin treatment with the modulation of purine metabolism, reduced microglial inflammatory responses, improved mitochondrial energy metabolism, and alleviation of fatigue symptoms in ME/CFS subjects: pilot findings from phase-II observational study.},
journal = {Journal of translational medicine},
year = {2026},
doi = {10.1186/s12967-026-08575-3},
note = {PubMed: 42432754},
url = {https://www.mecfsatlas.com/evidence/gile-2026-association-rapamycin},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-07-12. https://www.mecfsatlas.com/evidence/gile-2026-association-rapamycin
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