筋萎縮性側索硬化症（ALS）および希少筋疾患に対する治療法の開発

抄録

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder leading to respiratory muscle paralysis a few years after the onset because of motor neuron death. After the discovery of SOD1 in 1993 as the causative gene, more than 20 genes, such as FUS, the second most frequent in Japan, and C9ORF72, the most frequent in Europe and the United States, have been clarified. Based on the dying back hypothesis, we focused on axonal pathology of ALS. We developed microfluidic device system to elucidate the pathomechanism of axon fraction from patient–derived induced pluripotent stem (iPS) cells and its gene–editing isogenic controls. Key molecules in axonal pathology in the early stages of the disease are becoming clearer.

GNE myopathy is rare muscle disease affecting distal muscles like tibialis anterior. GNE gene, which encodes for a key enzyme in the sialic acid biosynthesis pathway, is mutated in the homozygote or compound heterozygote manner. The lack of sialic acid in skeletal muscle is the critical pathological process in GNE myopathy. GNE myopathy mouse model was established, and supplementation of sialic acid improves the phenotype of these models. Phase 1 clinical trial in Japan was conducted at Tohoku University Hospital using aceneuramic acid, followed by the trials using slow–release product. Phase II/III study, subsequent extended trial and confirmational trial were performed. Regulatory approval is currently under discussion.