Spinal muscular atrophy.
Spinal muscular atrophy.
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DOI：
10.1016/b978-0-444-64076-5.00038-7
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发表时间：
2018-01-01
影响因子：
--
通讯作者：
Fischbeck, Kenneth H
中科院分区：
文献类型：
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作者：
Arnold, Eveline S;Fischbeck, Kenneth H
常染色体隐性遗传性近端脊髓性肌萎缩症(Werdnig-Hoffmann，Kugelberg-Welander)是由SMN1基因突变引起的，其临床严重程度与一个几乎相同的基因SMN2的拷贝数有关。SMN蛋白在剪接体组装中起关键作用，并可能具有其他细胞功能，如mRNA运输。细胞培养和动物模型有助于确定疾病机制和确定治疗干预的目标。开发治疗方法的主要焦点一直是提高SMN水平，而通过小分子、寡核苷酸和基因替换来实现这一点已经相当成功。一种名为nusinesen的寡核苷酸最近被批准用于患者的治疗，其他药物的验证性研究目前正在进行中。
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.