NUSINERSEN ADVANCES IN SMA TREATMENT

Abstract

Spinal muscular atrophy (SMA) is a rare, autosomal recessive neuromuscular disorder caused by mutations or deletions in the SMN1 gene, leading to progressive motor neuron degeneration and muscle weakness. Nusinersen, an antisense oligonucleotide designed to modify SMN2 pre-mRNA splicing and increase functional SMN protein production, represents the first disease-modifying therapy approved for 5q SMA. This review summarizes evidence from pivotal clinical trials, including ENDEAR, CHERISH, EMBRACE, and DEVOTE, as well as real-world data in pediatric and adult populations. Across phenotypes, nusinersen has demonstrated clinically meaningful improvements or stabilization of motor function and increased survival free from permanent ventilation, particularly when initiated early in the disease course. Evidence suggests that treatment response may vary depending on baseline functional status and timing of therapy initiation. Despite proven efficacy, challenges remain, including limited long-term follow-up data, lack of direct head-to-head comparisons with other disease-modifying therapies, and variability in global accessibility due to economic and infrastructural factors. Additionally, manufacturing complexity and high production costs of antisense oligonucleotides influence healthcare system sustainability. Ongoing research focused on dosing optimization, long-term outcomes, and advances in oligonucleotide synthesis technologies may further refine the role of nusinersen within the evolving therapeutic landscape of SMA.