Arnold Eveline S, Fischbeck Kenneth H
Neurogenetics Branch, National Institutes of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States.
Neurogenetics Branch, National Institutes of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States.
Handb Clin Neurol. 2018;148:591-601. doi: 10.1016/B978-0-444-64076-5.00038-7.
Autosomal-recessive proximal spinal muscular atrophy (Werdnig-Hoffmann, Kugelberg-Welander) is caused by mutation of the SMN1 gene, and the clinical severity correlates with the number of copies of a nearly identical gene, SMN2. The SMN protein plays a critical role in spliceosome assembly and may have other cellular functions, such as mRNA transport. Cell culture and animal models have helped to define the disease mechanism and to identify targets for therapeutic intervention. The main focus for developing treatment has been to increase SMN levels, and accomplishing this with small molecules, oligonucleotides, and gene replacement has been quite. An oligonucleotide, nusinersen, was recently approved for treatment in patients, and confirmatory studies of other agents are now under way.
常染色体隐性遗传性近端脊髓性肌萎缩症（韦-霍二氏病、库-韦二氏病）由运动神经元存活基因1（SMN1）突变引起，临床严重程度与一个几乎相同的基因——运动神经元存活基因2（SMN2）的拷贝数相关。SMN蛋白在剪接体组装中起关键作用，可能还具有其他细胞功能，如mRNA转运。细胞培养和动物模型有助于明确疾病机制并确定治疗干预靶点。开发治疗方法的主要重点一直是提高SMN水平，通过小分子、寡核苷酸和基因替代来实现这一点已经取得了一定成果。一种寡核苷酸药物——诺西那生钠最近被批准用于治疗患者，其他药物的验证性研究正在进行中。
