Department of Veterinary Pathobiology, Bond Life Sciences Center, Room 440C, University of Missouri, Columbia, MO 65211, USA.
Future Med Chem. 2012 Oct;4(16):2067-84. doi: 10.4155/fmc.12.131.
Spinal muscular atrophy (SMA) is a leading genetic cause of infant mortality. A neurodegenerative disease, it is caused by loss of SMN1, although low, but essential, levels of SMN protein are produced by the nearly identical gene SMN2. While no effective treatment or therapy currently exists, a new wave of therapeutics has rapidly progressed from cell-based and preclinical animal models to the point where clinical trials have initiated for SMA-specific compounds. There are several reasons why SMA has moved relatively rapidly towards novel therapeutics, including: SMA is monogenic; the molecular understanding of SMN gene regulation has been building for nearly 20 years; and all SMA patients retain one or more copies of SMN2 that produces low levels of full-length, fully functional SMN protein. This review primarily focuses upon the biology behind the disease and examines SMN1- and SMN2-targeted therapeutics.
脊髓性肌萎缩症（SMA）是婴儿死亡的主要遗传原因。作为一种神经退行性疾病，它是由 SMN1 的缺失引起的，尽管 SMN2 基因也能产生低但至关重要的 SMN 蛋白水平。目前虽然尚无有效的治疗方法，但一波新的治疗方法已迅速从基于细胞和临床前动物模型发展到临床试验开始针对 SMA 特异性化合物的阶段。SMA 相对较快地发展为新型治疗方法有几个原因，包括：SMA 是单基因疾病；对 SMN 基因调控的分子理解已经建立了近 20 年；并且所有 SMA 患者都保留了一个或多个产生全长、功能齐全的 SMN 蛋白的低水平的 SMN2 拷贝。本综述主要关注疾病背后的生物学，并研究针对 SMN1 和 SMN2 的治疗方法。
