肌萎缩侧索硬化症（ALS）的治疗仍一筹莫展，其病因及发病机制在理论上认识十分有限。现有的研究ALS的动物模型不能完全真实、客观地反映人类ALS发病机制、限制了人们对ALS疾病"早期"阶段的研究。患者来源的可诱导的多潜能干细胞（iPSCs）可模拟神经系统多种变性疾病包括帕金森病及阿尔茨海默病。本研究拟用合作者美国威斯康辛大学张素春教授实验室建立的ALS 患者的iPSC 细胞系, 利用TALEN技术建立高效的iPSCs SOD1 点突变打靶体系，获得患者个性化的纠正突变的正常细胞，体外向运动神经元分化模仿运动神经元发育过程，从细胞水平及分子水平动态观察SOD1突变基因对运动神经元的影响，包括形态学、电生理、细胞轴浆运输、细胞凋亡的影响。试图寻找运动神经元变性的始因，探讨ALS病理性改变的启动与发病机制，为临床新药的筛选提供有力的理论依据。

The treatment Amyotrophic lateral sclerosis(ALS) is very tough till now because the etiology and pathogenesis of is inadequately understood, the animal models aren't able to reflect the human disease fully and objectively , which limit the study of early stage for ALS. Induced pluripotent stem cell can be used to model neurodegenerative disease including Parkinson and Alzheimer's disease. This study is planning to use the SOD1 mutant iPSCs lines from the collaboration professor Su-Chun Zhang in USA, apply the high targeted technical TALEN to correct the SOD1 mutant and get the isogenic cells, then differentiate the cells into motor neuron(MN), and detect the effect of SOD1 mutant on MN including morphology, electric physiology, transportation of axon and cell apoptosis, try to find the cause the MN degeneration, explore the initiation and pathogenesis of ALS, supply a strong .evidence for novel drug screen for clinic application.