Long-term real-world outcomes of nusinersen treatment in patients with spinal muscular atrophy types I-III

BACKGROUND: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by mutations or deletions in the survival motor neuron 1 (SMN) gene, with disease severity influenced by SMN2 copy number. Nusinersen, an antisense oligonucleotide therapy, has emerged as an effective treatment option. This study aimed to evaluate the long-term clinical outcomes of nusinersen treatment in SMA patients. METHODS: Patients with SMA types I-III who received nusinersen between 2017 and 2024 were retrospectively analyzed. SMA type I patients were evaluated using the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), while types II and III were followed with the Hammersmith Functional Motor Scale-Expanded (HFMSE). RESULTS: In SMA Type II (n = 11; mean age 17.8 ± 5.7 years), mean HFMSE scores improved from 11.3 ± 16.3 to 14.1 ± 17.4 after fourth dose. In SMA Type III patients (n = 9; mean age 20.2 ± 6.4 years), scores improved from 38.8 ± 22.1 to 43.0 ± 21.8. Linear mixed-effects analysis demonstrated a significant association between cumulative nusinersen dose and improved motor function (p < 0.001). Clinically meaningful improvement was maintained in 75% of patients with SMA types II and III at the final follow-up, whereas outcomes in SMA type I were heterogeneous and could not be interpreted conclusively because of the small sample size, late treatment initiation, and advanced disease severity. CONCLUSION: Nusinersen was associated with early motor improvement and long-term stabilization, a clinically meaningful outcome given the progressive nature of SMA.