Faculty of Rehabilitation, Kobe Gakuin University, 518 Arise, Ikawadani-cho, Nishi-ku, Kobe 651-2180, Japan.
Laboratory of Molecular and Biochemical Research, Biomedical Research Core Facilities, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Int J Mol Sci. 2023 Jul 26;24(15):11939. doi: 10.3390/ijms241511939.
Spinal muscular atrophy (SMA) is a lower motor neuron disease with autosomal recessive inheritance. The first cases of SMA were reported by Werdnig in 1891. Although the phenotypic variation of SMA led to controversy regarding the clinical entity of the disease, the genetic homogeneity of SMA was proved in 1990. Five years later, in 1995, the gene responsible for SMA, , was identified. Genetic testing of has enabled precise epidemiological studies, revealing that SMA occurs in 1 of 10,000 to 20,000 live births and that more than 95% of affected patients are homozygous for deletion. In 2016, nusinersen was the first drug approved for treatment of SMA in the United States. Two other drugs were subsequently approved: onasemnogene abeparvovec and risdiplam. Clinical trials with these drugs targeting patients with pre-symptomatic SMA (those who were diagnosed by genetic testing but showed no symptoms) revealed that such patients could achieve the milestones of independent sitting and/or walking. Following the great success of these trials, population-based newborn screening programs for SMA (more precisely, -deleted SMA) have been increasingly implemented worldwide. Early detection by newborn screening and early treatment with new drugs are expected to soon become the standards in the field of SMA.
脊髓性肌萎缩症（SMA）是一种常染色体隐性遗传的下运动神经元疾病。SMA 的首例病例由 Werdnig 于 1891 年报告。尽管 SMA 的表型变异导致了对该疾病临床实体的争议，但 SMA 的遗传同质性在 1990 年得到了证明。五年后，即 1995 年，确定了导致 SMA 的基因 。对 进行的基因检测使精确的流行病学研究成为可能，揭示 SMA 的发病率为每 10000 至 20000 例活产儿中有 1 例，并且超过 95%的受影响患者为 缺失纯合子。2016 年，nusinersen 成为美国首个批准用于治疗 SMA 的药物。随后又批准了另外两种药物：onasemnogene abeparvovec 和 risdiplam。针对有症状前 SMA 患者（通过基因检测诊断但无症状的患者）的这些药物的临床试验表明，这些患者可以达到独立坐和/或行走的里程碑。鉴于这些试验的巨大成功，全球范围内越来越多地实施了针对 SMA（更确切地说是 - 缺失型 SMA）的基于人群的新生儿筛查计划。通过新生儿筛查尽早发现和使用新药进行早期治疗有望很快成为 SMA 领域的标准。
