Drug Repurposing
COMPUTATIONALDrug repurposing means finding new therapeutic uses for existing approved drugs — bypassing the 10–15 years and $1–2B typically required for de novo drug development. Repurposed drugs have already passed safety trials, so clinical translation is dramatically faster: Phase I is often skipped and Phase II can start in 2–3 years rather than 10+.
The platform identifies SMA repurposing candidates through three convergent strategies: (1) Cross-disease mining — drugs approved or in trials for related neuromuscular diseases (ALS, Duchenne Muscular Dystrophy, SBMA, CMT) that share molecular targets with SMA; (2) ChEMBL bioactivity — known compounds with high pChEMBL values (≥ 6.0, corresponding to IC₅₀ ≤ 1 µM) against top-scored SMA targets; (3) Pathway overlap — compounds whose known mechanism overlaps with the actin dynamics, NMJ signaling, or autophagy/survival pathways dysregulated in SMA.
▶How does Repurposing Scoring work?
Each candidate is scored 0–1 based on target relevance, potency, clinical phase, and pathway convergence. Three convergent strategies: (1) Cross-disease mining — drugs approved/in trials for related neuromuscular diseases sharing SMA targets; (2) ChEMBL bioactivity — compounds with pChEMBL ≥ 6.0 (IC₅₀ ≤ 1 µM) against SMA targets; (3) Pathway overlap — mechanism overlaps SMA-relevant pathways.
Precedent: Valproic acid (HDAC inhibitor, epilepsy origin) was one of the first SMA trial compounds. Olesoxime reached Phase II. Riluzole (ALS) showed modest motor neuron protection in SMA models. The platform extends this approach computationally. Click any row to see full rationale, mechanism, and target link.