Treatment for Spinal Muscular Atrophy Using Onasemnogene Abeparvovec

Abstract

Spinal muscular atrophy (SMA) is the most common cause of death in infancy. Recently introduced molecular-based approaches have changed the poor prognosis, saved lives and improved the quality of life for those affected with SMA. Gene therapy uses an adeno-associated virus (AAV) to deliver and replace the mutant survival of motor neuron (SMN ) genes, SMN1 and SMN2. This review describes the development, relative safety and efficacy of intravenously delivered AAV for SMA type 1 and the intrathecal delivery for SMA type 2. For SMA, viral immunosuppressive treatment and AAV doses never used in clinical research or practice were required for success. As a prototype, the approach has greatly influenced the development of treatment for other childhood and adult diseases. Two additional pharmacologic agents, nusinersen and risdiplam, are clinically approved as alternative treatments. Both use antisense oligonucleotides and are briefly described in this review.