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

Brooke Gile, Sarojini Bulbule, Mubaraq A Toriola, Brian T Ruan, Shabnam Marium, Anna Benko, Stephanie Grach, Michael Mueller, Lucinda Bateman, Jennifer Bell, Brayden Yellman, Jon Berner, Bela Chheda, David Kaufman, Gunnar Gottschalk, Avik Roy · 2026 · Journal of Translational Medicine · Atlas ID GIL2026

Low-dose rapamycin in ME/CFS patients reduced fatigue symptoms, modulated purine biosynthesis via IMP dehydrogenase inhibition, reduced microglial inflammatory responses, and improved mitochondrial energy metabolism in a phase-II observational pilot study.

At a glance

Evidence tierB Direct human evidence
Study type3 - Human Observational
Model systemHuman (ME/CFS patients)
JournalJournal of Translational Medicine
Year2026
Peer reviewedYes
SourceDOI 10.1186/s12967-026-08575-3 · PMID 42432754 · Free full text (PMC13374298)

Abstract

Phase II observational pilot trial. Low-dose rapamycin significantly reduced fatigue symptoms in ME/CFS subjects. LCMS-based quantification revealed differential regulation of purine biosynthetic intermediates (IMP to XMP and HPX pathway). Rapamycin reduces IMP dehydrogenase activity, limiting IMP to XMP conversion. Altered purine levels impair mitochondrial energy metabolism and contribute to microglial inflammation. No placebo group; results biased to responders. NCT06257420.

Extracted findings

InterventionLow-dose rapamycin
TargetmTORC1 / IMP dehydrogenase / purine biosynthesis / mitochondria
ModelHuman
EffectReduced fatigue, improved mitochondrial energy metabolism, modulated purine biosynthesis, reduced microglial inflammation

Related topics

mTORC1RapamycinLongevityULK1

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