Nusinersen vs. Sham Control in Infantile-Onset Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disease caused by homozygous deletion of the SMN1 gene, producing insufficient survival motor neuron (SMN) protein. A paralogous SMN2 gene also encodes SMN protein. Because 90% of SMN2 messenger RNAs are degraded, severity of the SMA phenotype correlates with SMN2 copy number. Individuals with type I SMA, the most common and severe form, typically possess two SMN2 copies. They are profoundly weak, have symptom onset before age 6 months, and have life expectancy less than 2 years of age without respiratory support.

Researchers conducted a randomized, double-blind, sham-controlled, manufacturer-funded phase 3 study of efficacy and safety of nusinersen, an antisense oligonucle…