Identification of drug repurposing candidates for amyotrophic lateral sclerosis using electronic health records: a retrospective cohort study - PubMed
12 hours ago
- #electronic health records
- #ALS
- #drug repurposing
- The study aimed to identify drug repurposing candidates for Amyotrophic Lateral Sclerosis (ALS) using electronic health records (EHRs) from the US Veterans Health Administration (VHA).
- A retrospective cohort analysis was conducted on 11,003 individuals diagnosed with ALS between 2009 and 2019, focusing on medication effects post-diagnosis.
- Two exposure criteria were used to assess medication effects: Criteria A required medication dispense within 12 months of diagnosis and at least 6 months of use; Criteria B required at least two dispenses within 6 months before and 12 months after diagnosis.
- Propensity score-matched control groups were created to infer treatment effects, with the primary outcome being death, analyzed using Cox proportional hazards models.
- 27 out of 162 medications analyzed showed statistically significant changes in hazard ratios (HR) for death, with 18 associated with reduced HR (prolonged survival) and 9 with increased HR (reduced survival).
- Drugs associated with prolonged survival included HMG-CoA reductase inhibitors (e.g., simvastatin), PDE5 inhibitors (e.g., sildenafil), and α-adrenergic antagonists (e.g., tamsulosin).
- PathFx analysis identified a protein network complex interacting with several drugs, suggesting potential therapeutic targets for ALS.
- The study is the largest EHR-based analysis for ALS drug repurposing, identifying promising candidates for further therapeutic assessment.
- Funding was provided by the Congressionally Directed Medical Research Programs, US Department of Defense, with some authors declaring no competing interests except for travel and research funding disclosures.