Treatment of Spinal Muscular Atrophy

Abstract

Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease that predominantly affects motor neurons, resulting in progressive muscular atrophy and weakness. SMA arises due to insufficient levels of the survival motor neuron (SMN) protein as a result of homozygous disruption of the SMN1 gene. The SMN protein is also produced by the paralogous gene SMN2, but the amount of SMN produced is minimal due to a defect in the splicing process. Nusinersen, an antisense oligonucleotide, and risdiplam, an oral small molecule, have been developed to repair SMN2 splicing failures to facilitate adequate production of the SMN protein. Onasemnogene abeparvovec utilizes a nonreplicating adeno-associated virus 9 to provide a copy of the gene encoding the SMN protein. This therapy has led to a dramatic advancement in SMA treatment. Here, we introduce current treatment strategies for SMA.