脊髓性肌萎缩症的治疗进展
Treatment Advances in Spinal Muscular Atrophy.
作者信息
Bharucha-Goebel Diana, Kaufmann Petra
机构信息
Department of Neurology, Children's National Medical Center, Washington, DC, USA.
Neuromuscular and Neurogenetic Disorders of Childhoood Section (NNDCS)/NINDS/NIH, Bethesda, MD, USA.
出版信息
Curr Neurol Neurosci Rep. 2017 Oct 6;17(11):91. doi: 10.1007/s11910-017-0798-y.
PURPOSE OF REVIEW
Spinal muscular atrophy (SMA) is a genetic disorder of motor neurons in the anterior horns of the spinal cord and brainstem that results in muscle atrophy and weakness. SMA is an autosomal recessive disease linked to deletions of the SMN1 gene on chromosome 5q. Humans have a duplicate gene (SMN2) whose product can mitigate disease severity, leading to the variability in severity and age of onset of disease, and is therefore a target for drug development.
RECENT FINDINGS
Advances in preclinical and clinical trials have paved the way for novel therapeutic options for SMA patients, including many currently in clinical trials. In 2016, the first treatment for SMA has been approved in the USA, an antisense oligonucleotide that increases full-length protein product derived from SMN2. The approval of a first treatment for SMA and the rapid advances in clinical trials provide the prospect for multiple approaches to disease modification. There are several other promising therapeutics in different stages of development, based on approaches such as neuroprotection, or gene therapy.
综述目的
脊髓性肌萎缩症（SMA）是一种脊髓前角和脑干运动神经元的遗传性疾病，可导致肌肉萎缩和无力。SMA是一种常染色体隐性疾病，与5号染色体上SMN1基因的缺失有关。人类有一个重复基因（SMN2），其产物可减轻疾病严重程度，导致疾病严重程度和发病年龄的变异性，因此是药物开发的靶点。
最新发现
临床前和临床试验的进展为SMA患者的新型治疗选择铺平了道路，包括许多目前正在进行的临床试验。2016年，美国批准了首个用于SMA的治疗药物，一种反义寡核苷酸，可增加源自SMN2的全长蛋白产物。首个SMA治疗药物的获批以及临床试验的快速进展为多种疾病修饰方法带来了前景。基于神经保护或基因治疗等方法，还有其他几种有前景的治疗药物正处于不同的开发阶段。
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