新しい時代を迎えた脊髄性筋萎縮症の治療

抄録

Spinal muscular atrophy (SMA) is an autosomal recessive genetic disorder characterized by degeneration of the anterior horn of the spinal cord and muscle atrophy, most commonly caused by the survival motor neuron 1 (SMN1) on chromosome 5 (5q13). The severity ranges according to time of onset and is classified as type 0–4. SMN2 is paralogous to SMN1, and the copy number of the SMN2 is an important determinant of SMA severity. That is, a greater number of SMN2 copies can generate more SMN protein and presents milder SMA phenotypes. A series of novel therapies have been approved for SMA in recent years, which include nusinersen, a nucleic acid drug using antisense oligonucleotides ; onasemnogene abeparvovec–xioi, a gene therapy drug ; and risidiplam, a small molecule drug. Each has different routes and intervals of administration, but all are designed to increase SMN protein. Clinical trials have shown positive effect on survival, respiratory function, as well as motor function. In order to achieve higher efficacy, evidences have shown that initiation of the treatment as early as possible is essential. In this term, a newborn screening system is being developed for early diagnosis. The further accumulation of data to assess the long–term efficacy and safety of these drugs are needed.