Evidence map›Paper›PMID 41121328›Full record

Observational studyJournal of translational medicine2025

Low-dose rapamycin alleviates clinical symptoms of fatigue and PEM in ME/CFS patients via improvement of autophagy: a pilot study.

Brian T Ruan, Sarojini Bulbule, Brooke Gile, Amy Reyes, Bela Chheda, Lucinda Bateman, Jennifer Bell, Brayden Yellman, Stephanie L Grach, Jon Berner and 4 more

Registry-linked trialAbstract readMulticenter StudyObservational Study
In one paragraph

Observational study in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06257420 (Low Dose Rapamycin in ME/CFS, Long-COVID, and Other Infection Associated Chronic Conditions), which is not on this map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT06257420 enrolling by invitationnot on this map

Low Dose Rapamycin in ME/CFS, Long-COVID, and Other Infection Associated Chronic Conditions

TypeobservationalSponsorSimmaron Research Inc.Ran2023 to 2027Enrolled150ConditionsMyalgic Encephalomyelitis, Long-COVIDArmsRapamycin
3 · Its place in the literature

Who cites it

13 citing papers in PubMed.

  1. Trial
  2. Review
  3. From lipid overload to autophagy collapse: how lipid dysregulation drives chronic inflammation and metabolic disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Review
  4. Article
  5. Article
  6. Article
  7. An Overview of Severe Myalgic Encephalomyelitis.Journal of clinical medicine · 2026
    Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Brian T RuanCornell EIND Center, Cornell University, Ithaca, NY, USA.ORCID 0009-0008-1330-6806
Sarojini BulbuleResearch and Development Lab, Simmaron Research Inc., University of Wisconsin-Milwaukee, Milwaukee, USA.
Brooke GileResearch and Development Lab, Simmaron Research Inc., University of Wisconsin-Milwaukee, Milwaukee, USA.
Amy ReyesResearch and Development Lab, Simmaron Research Inc., University of Wisconsin-Milwaukee, Milwaukee, USA.
Bela ChhedaCenter for Complex Diseases, Palo Alto, CA, USA.
Lucinda BatemanBateman Horne Center, Salt Lake City, UT, USA.
Jennifer BellBateman Horne Center, Salt Lake City, UT, USA.
Brayden YellmanBateman Horne Center, Salt Lake City, UT, USA.
Stephanie L GrachMayo Clinic, Rochester, MN, USA.
Jon BernerWoodinville Psychiatry, Woodinville, WA, USA.
Daniel L PetersonSierra Internal Medicine, Incline Village, NV, USA.
David KaufmanCenter for Complex Diseases, Seattle, WA, USA. david@centerforcomplexdiseases.com.
Avik RoyResearch and Development Lab, Simmaron Research Inc., University of Wisconsin-Milwaukee, Milwaukee, USA. aroy@simmaron.com.ORCID 0000-0003-0523-8504
C Gunnar GottschalkResearch and Development Lab, Simmaron Research Inc., University of Wisconsin-Milwaukee, Milwaukee, USA. ggottschalk@simmaron.com.

Funding

Clinical and Translational Science AwardUL1TR001873 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI REILLY, MUREDACH P · 2016 to 2025
$99.0M
Disparities in COVID Disease Severity and Outcomes in New York CityUL1TR002384 · NCATS · WEILL MEDICAL COLL OF CORNELL UNIV · PI JULIANNE L IMPERATO-MCGINLEY · 2017 to 2026
$86.2M
ATG13: A new player in ME/CFSR21NS129021 · NINDS · SIMMARON RESEARCH INC · PI ROY, AVIK · 2023 to 2024
$450k
Khosla Ventures Khosla VenturesNCATS NIH HHS UL1 TR001873NCATS NIH HHS UL1 TR002384NINDS NIH HHS R21 NS129021NINDS NIH HHS R21NS129021-01A1Solve ME/CFS Initiative Ramsay AwardSybille Hesse Foundation Sybille Hesse Foundation
6 · The paper itself

Abstract

snippets

backgroundmTOR activation is associated with chronic inflammation in ME/CFS. Previous studies have shown that sustained mTOR activation may cause chronic muscle fatigue by inhibiting ATG13-mediated autophagy. However, the therapeutic implication of this finding has not been established. Given that rapamycin is an mTOR inhibitor, this study aims to investigate whether low-dose rapamycin treatment improves autophagy markers and clinical symptoms of fatigue in ME/CFS subjects. This highlights the pivotal role of mTOR in the pathogenesis of ME/CFS.

methodsWe conducted a decentralized, uncontrolled trial of rapamycin in 86 patients with ME/CFS to evaluate its safety and efficacy. Low-dose rapamycin (6 mg/week) was administered, and core ME/CFS symptoms were assessed on days 30 (T1), 60 (T2), and 90 (T3). Plasma levels of autophagy metabolites, such as pSer258-ATG13 and BECLIN-1, were measured and correlated with clinical outcomes, specifically MFI.

resultsRapamycin (6 mg/week) was tolerated without any SAEs. Of the 70 patients who completed at the minimum to T1, 52 (74.3%) showed recovery in fatigue, PEM, and OI, along with improvements in MFI fatigue domains and SF-36 aspects. High levels of BECLIN-1 were detected in T3. Plasma pSer258-ATG13 levels were strongly downregulated at T1. Spearman's correlation analysis indicated an association between autophagy impairment and reduced activity.

conclusionsLow-dose rapamycin effectively reduced PEM and other key symptoms in patients with ME/CFS, as measured by BAS, SSS, MFI, and SF-36. Future studies should encompass dose optimization and develop a diagnostic tool to identify responders with mTOR-mediated autophagy disruption.

Indexed as

AutophagyFatigueFatigue Syndrome, ChronicSirolimusAdultDose-Response Relationship, DrugFemaleHumansMaleMiddle AgedPilot ProjectsTreatment OutcomeSirolimus

Identifiers

PMID41121328
PMCPMC12538759

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.