The evolving therapeutic landscape of spinal muscular atrophy – A scoping review of investigational agents, emerging delivery technologies and strategic innovations

Spinal muscular atrophy (SMA) is a severe neuromuscular disease with emerging therapeutic complexity. This review aims to systematically map the global pipeline of investigational treatments for SMA. Using ClinicalTrials.gov and complementary international registries, we identified 21 planned or ongoing interventional trials from 2020 to 2025 targeting novel agents, alternative dosing and delivery routes. Inclusion criteria focused on unapproved therapies or new uses of existing drugs, with rigorous data extraction across demographics, modalities and trial phases. Results reveal a shift towards dual-pronged strategies: refining SMN-targeted interventions and expanding SMN-independent approaches, such as myostatin inhibitors, neuromuscular modulators and ion-channel blockers. Early-phase outcomes suggest promising motor function improvements and acceptable safety profiles, though long-term efficacy remains under investigation. This evolving landscape underscores the importance of registry-based analyses in tracking translational innovation, informing stakeholders and guiding future research priorities.