[Familial Amyotrophic Lateral Sclerosis]

Amyotrophic lateral sclerosis (ALS) is the most rapidly progressive motor neuron disease (MND) in adults, characterized by the selective death of motor neurons in the motor cortex, brainstem, and spinal cord. Riluzole and edaravone are the only approved drugs available in Japan to date. Approximately 10% of ALS cases are familial in rature, defined as the existence of disease-causing mutation. SOD1 is the most frequent causative gene for ALS among Japanese individuals, while C9orf72 mutation is more prevalent in Western countries. Genotype-phenotype correlation described in the literature of familial ALS enables to establish models of the disease. This review article describes the clinical characteristics of familial ALS based on each disease-causing mutation. The pathomechanism of ALS including proteostasis, RNA metabolism, and axonal pathology are discussed in detail. We also reviewed the status of development of therapeutic strategies for familial ALS based on analysis of animal models and induced pluripotent stem cells.