Antisense therapy of spinal muscular atrophy ―beyond the achievement―

Abstract

Loss–of–function mutations in SMN1 cause spinal muscular atrophy (SMA), a leading genetic cause of infant mortality. Humans have a closely related SMN2, but it only expresses low levels of SMN protein, due to alternative splicing. Based on clinical trials showing a significant increase in survival and motor development in SMA infants and children, an SMN2 splicing–correcting antisense oligonucleotide has been approved as the disease–modifying drug for SMA. Development of therapies and advanced medical care have dramatically improved the prognosis of SMA. Collected clinical data will allow filling the current gaps in our knowledge of SMA natural history during adult life and the drug efficacy especially for long–term chronic progressors.