Emerging therapeutic strategies and clinical management of spinal muscular atrophy

Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder characterized by degeneration of spinal motor neurons due to loss of SMN1 gene function, with disease severity influenced by SMN2 copy number. This review aims to summarize the current understanding of SMA pathogenesis, diagnostic approaches, and the evolving landscape of SMN-dependent therapeutic strategies, including antisense oligonucleotide therapy, small molecule splicing modifiers, and gene replacement therapy, while highlighting implications for clinical outcomes and early intervention.

A systematic literature search was conducted across the databases of Gene Reviews, PubMed, Brain Sciences, Science Direct, and the search engine Google Scholar to identify studies on SMA. Relevant studies addressing SMN1/SMN2 mechanisms, clinical types, and current SMN-enhancing therapies were screened. Published evidence relating to SMA epidemiology in India, Japan, and the global population was examined alongside data on FDA-approved treatments. Eligible studies meeting these criteria were included in the review.

SMA results from biallelic SMN1 disruption, leading to insufficient SMN protein for motor neuron survival. SMN2 copy number predicts disease phenotype. Advances in molecular biology have produced three disease-modifying treatments that increase SMN protein or replace SMN1 function. Adjunct therapies targeting muscle function show early but limited benefits.

Early newborn screening, carrier detection, and timely intervention are expected to significantly improve SMA incidence, presentation, and prognosis. Despite progress with gene replacement and SMN2-modifying therapies, further research is needed to optimize outcomes and assess long-term effectiveness.