Nusinersen safety and effects in children with spinal muscular atrophy: a single center experience

Objective Spinal muscular atrophy (SMA) is a genetic motor neuron disorder characterized by progressive muscle atrophy. Nusinersen, an antisense oligonucleotide that promotes production of the functional survival motor neuron protein is approved for the treatment of SMA 5q in China in 2019.Our aims were to investigate safety and efficacy of nusinersen in children with spinal muscular atrophy (SMA). Methods This prospective study included all children with SMA who attended our multidisciplinary SMA clinic and received Nusinersen treatment during 10/2019-2/2022. We documented prospectively clinical data including mutational analysis of SMN1 and SMN2 genes, ventilatory and nutritional status, complications, and motor function outcomes as measured on a standardized scales at baseline and follow-up. Results We included 22 patients (3 SMA 1, 15 SMA 2 and 3 SMA 3）with median age at first administration of 3.9 years(range 0.7-10.4 years). The mutational analysis revealed three SMN2 gene copies in the majority of patients (90.9%). Median disease duration was 40.5 months. All of the patients shows stable or improvement in HINE2 score. 2 SMA 1 patients gained great change in CHOP INTEND score. The patients with shorter disease duration tended to show greater improvement over time in SMA type2 patients. SMA 3 patients(2/4) gained great change in HSMSE score. During the follow-up, Nusinersen was well tolerated, and no new safety findings were identified. Conclusions Our data provide further evidence of nusinersen safety and efficacy in SMA patients. In patients with extremely advance disease, effects on residual motor function are less clear.