Progress in spinal muscular atrophy research.

PURPOSE OF REVIEW: The development of new therapies has brought spinal muscular atrophy (SMA) into the spotlight. However, this was preceded by a long journey - from the first clinical description to the discovery of the genetic cause to molecular mechanisms of RNA and DNA technology.

RECENT FINDINGS: Since 2016, the antisense oligonucleotide nusinersen has been (FDA) approved for the treatment of SMA, followed by the gene replacement therapy onasemnogene abeparvovec-xioi in 2019 and the small-molecule risdiplam in 2020. These drugs, all targeting upregulation of the SMN protein not only showed remarkable effects in clinical trials but also in real-world settings. SMA has been implemented in newborn screening in many countries around the world. SMN-independent strategies targeting skeletal muscle, for example, may play another therapeutic approach in the future.

SUMMARY: This review aims to summarize the major clinical and basic science achievements in the field of SMA.