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Publications

Journal Article Preprint Epublish 2 citations

PubMed: 40502741 DOI: 10.21203/rs.3.rs-6596158/v1

Low Dose Rapamycin Alleviates Clinical Symptoms of Fatigue and PEM in ME/CFS Patients via Improvement of Autophagy.

Res Sq

Authors: Brian T Ruan, Sarojini Bulbule, Amy Reyes, Bela Chheda, Lucinda Bateman, Jennifer Bell, Braydon Yellman, Stephanie Grach, Jon Berner, Daniel L Peterson, David Kaufman, Avik Roy, C Gunnar Gottschalk

Affiliations

  • Cornell University.
  • Simmaron Research INC.
  • University of Wisconsin-Milwaukee.
  • Center for Complex Diseases, Palo Alto, CA.
  • Bateman Horne Center.
  • Mayo Clinic Research Rochester.
  • Woodinville psychiatric Associates.
  • Sierra Internal Medicine.
  • Center for Complex Diseases.

Abstract

Background

mTOR activation is associated with chronic inflammation in ME/CFS. Previous studies have shown that sustained mTOR activation can cause chronic muscle fatigue by inhibiting ATG13-mediated autophagy. This highlights the pivotal role of mTOR in the pathogenesis of ME/CFS.

Methods

We 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.

Results

Rapamycin (6 mg/week) was tolerated without any SAEs. Of the 40 patients, 29 (72.5%) showed strong recovery in PEM, fatigue, 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.

Conclusions

Low-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.

MeSH

Autophagy, Sirolimus, Signs And Symptoms, Fatigue