Rapamycin Treatment for Alzheimer's Disease and Related Dementias: A Pilot Phase 1 Clinical Trial

Strategic Insights -

Alzheimer's disease researchers at the University of Texas Health Science Center San Antonio have conducted a pilot phase 1 clinical trial to investigate the effects of rapamycin on humans. Although rapamycin has shown potential in extending lifespan and treating pathologies in animal models, its clinical application remains underexplored. The trial aimed to evaluate rapamycin's central nervous system penetrance and assess its safety, cognition, and effects on Alzheimer's disease and inflammatory biomarkers in the cerebrospinal fluid and plasma.

Key Takeaways:

  • The trial involved ten participants, aged 55-85 years old, with mild cognitive impairment or early-stage dementia, who received rapamycin 1 mg/day for eight weeks.
  • Rapamycin was not detectable in the cerebrospinal fluid before or after treatment, indicating its poor penetrance into the central nervous system.
  • Twenty, mostly mild adverse events occurred after treatment, including systolic blood pressure and hemoglobin A1c increase, and multiple erythrocyte parameters decrease.
  • There were no significant cognitive changes observed in the participants after treatment.
  • Several Alzheimer's disease and inflammatory biomarkers, including phosphorylated tau-181, glial fibrillary acidic protein, neurofilament light, interferon gamma, interleukin 5, vascular endothelial growth factor D, soluble fms-like tyrosine kinase-1, and placental growth factor, significantly increased after treatment.
  • The results highlight the need to better understand the biological effects and clinical impact of repurposing rapamycin for Alzheimer's disease.

Statistics:

  • 10 participants were involved in the trial.
  • The participants had a mean age of 74 ± 4 years, with 60% being female.
  • 20 adverse events occurred after treatment.
  • The percentage increase for systolic blood pressure after treatment was not specified in the original text.
  • The percentage increase for hemoglobin A1c after treatment was not specified in the original text.
  • The decrease in multiple erythrocyte parameters after treatment was not quantified.
  • 5 biomarkers (phosphorylated tau-181, glial fibrillary acidic protein, neurofilament light, interferon gamma, and interleukin 5) increased by a minimum of 0.70-4.59, 3787.44-9373.84, 204.28-561.61, 3.01-5.74, and 0.12-0.64 pg/ml respectively, 6,262.21 and 367.19 units, respectively, 4.37 units, and 0.33 units, respectively, after treatment.

Sources:

  • Rapamycin treatment for Alzheimer's disease and related dementias: a pilot phase 1 clinical trial. Communications Medicine, 2025, 5(1):1-12. The publisher for Communications Medicine is Nature Portfolio. A free version of this journal article is available at https://doi.org/10.1038/s43856-025-00904-9.