Scholarlink

Background <p>mTOR 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.</p> Methods <p>We conducted a decentralized, uncontrolled trial of rapamycin in 86 patients with ME/CFS to evaluate its safety and efficacy. Low-dose rapamycin (6&#xa0;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.</p> Results <p>Rapamycin (6&#xa0;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.</p> Conclusions <p>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.</p> Graphical Abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月21日

查看全文
  • Brian T. Ruan,
  • Sarojini Bulbule,
  • Brooke Gile,
  • Amy Reyes,
  • Bela Chheda,
  • Lucinda Bateman,
  • Jennifer Bell,
  • Brayden Yellman,
  • Stephanie L. Grach,
  • Jon Berner,
  • Daniel L. Peterson,
  • David Kaufman,
  • Avik Roy,
  • C. Gunnar Gottschalk

摘要

Background

mTOR 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.

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 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.

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.

Graphical Abstract