Spinal muscular atrophy: history and current treatment landscape
TL;DR
An overview of the history of SMA is provided, highlighting its evolving classification and the genetic basis underlying its clinical variability, and the development and clinical trial data of the three Food and Drug Administration- and European Medicines Agency-approved therapies: nusinersen, onasemnogene abeparvovec, and risdiplam are outlined.
Abstract
In recent years, pediatric neurology has witnessed significant advances in the development of disease-modifying therapies, with spinal muscular atrophy (SMA) emerging as one of the most impactful conditions in this field. This article provides a comprehensive overview of the history of SMA, highlighting its evolving classification and the genetic basis underlying its clinical variability. Moreover, it outlines the development and clinical trial data of the three Food and Drug Administration- and European Medicines Agency-approved therapies: nusinersen, onasemnogene abeparvovec, and risdiplam. These treatments have shifted SMA from a fatal diagnosis to a treatable condition, especially when initiated presymptomatically. Finally, the article discusses future directions, including combination therapies, novel pharmacological targets, biomarker development, and the need for ethical and equitable access to treatment worldwide. With ongoing research, SMA continues to serve as a paradigm for progress in neuromuscular medicine and the potential of personalized, gene-targeted therapies.