脊髄性筋萎縮症の新たな医療フェーズ

抄録

Loss–of–function mutations in SMN1 cause spinal muscular atrophy (SMA), the leading genetic cause of infant mortality. Humans have an SMN1 paralog, SMN2, but it only expresses low levels of SMN protein, due to alternative splicing. Based on clinical trials showing a significant effect on survival and motor achievemt in infants and children with SMA, three SMN restoration therapies, nusinersen, risdiplam, and onasemnogene abeparvovec, have been approved for both symptomatic and presymptomatic patients. Development of therapies and advanced clinical care have been improving the prognosis of SMA, and thus pediatric patients are increasingly surviving into adulthood. Longitudinal analyses of the collected data will allow filling the current gaps in our knowledge of SMA natural history and the therapeutic efficacy for patients during adult life. Furthermore, a study aiming to discover prognostic and drug–response biomarkers will aid in a better understanding of the pathophysiology of SMA and hopefully overcome some of the potential therapeutic limitations, especially for long–term chronic progressors.