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

Gile B, Bulbule S, Toriola MA, Ruan BT, Marium S, Benko A, Grach S, Mueller M, Bateman L, Bell J, Yellman B, …, Roy A · 2026 · Journal of Translational Medicine · Atlas ID GIL2026

What this study shows

In an uncontrolled phase-II pilot (no placebo), low-dose rapamycin was associated with reduced fatigue in ME/CFS. In plasma from responders, purine intermediates shifted, consistent with lower IMP dehydrogenase activity in PBMCs. Lab assays suggest that altered purines can impair mitochondrial metabolism and promote microglial inflammation; these links were not measured in patients.

Abstract

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In our ongoing phase II observational pilot trial, the compounded formulation of low-dose rapamycin significantly reduced fatigue-related clinical symptoms in ME/CFS subjects. Although the underlying molecular mechanism remains unclear, exploring metabolic pathways involving circulating blood-borne factors is warranted. Recent studies suggest that increased levels of purines may exacerbate oxidative stress in ME/CFS patients. It is not known if rapamycin modulates purine biosynthesis and improves disease symptoms.

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At a glance

Evidence type	H Human study Marked H because it is direct evidence from a human clinical trial or human cohort; the code names the kind of study, not its quality -- a small, well-run trial is still H.
Study type	3 - Human Observational
Model system	Human (ME/CFS patients)
Journal	Journal of Translational Medicine
Year	2026
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1186/s12967-026-08575-3 · PMID 42432754 · Free full text (PMC13374298)

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	Low-dose rapamycin
Target	mTORC1 / IMP dehydrogenase / purine biosynthesis / mitochondria
Model	Human
Effect	Reduced fatigue, improved mitochondrial energy metabolism, modulated purine biosynthesis, reduced microglial inflammation

In the Atlas

Answers that reference this study

Discussed in the plain-language answer What are rapamycin's side effects?.

Cite this paper

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Gile, B., Bulbule, S., Toriola, M. A., Ruan, B. T., Marium, S., Benko, A., Grach, S., Mueller, M., Bateman, L., Bell, J., Yellman, B., Berner, J., Chheda, B., Kaufman, D., Gottschalk, G., & Roy, A. (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

@article{GIL2026,
  author       = {Gile, B. and Bulbule, S. and Toriola, M. A. and Ruan, B. T. and Marium, S. and Benko, A. and Grach, S. and Mueller, M. and Bateman, L. and Bell, J. and Yellman, B. and Berner, J. and Chheda, B. and Kaufman, D. and Gottschalk, G. and Roy, A.},
  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         = {PMID: 42432754},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record GIL2026) [Data set]. https://mtor-atlas.org/study/GIL2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_GIL2026,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record GIL2026},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/GIL2026/},
  doi          = {10.5281/zenodo.22059963}
}

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