2025 年 42 巻 3 号 p. 377-381
Approximately 5% of people who develop ALS have a familial history, and most cases are inherited in an autosomal dominant manner. Last year in the United States, tofersen was rapidly approved for the treatment of familial ALS caused by mutations in the Cu/Zn superoxide dismutase (SOD1) gene. The practical application of Nusinersen for spinal muscular atrophy in 2016 was a major breakthrough in the field of neurological diseases, but it can be said that we are on the eve of a paradigm shift in treatment strategies for ALS as well. Target genes for antisense oligos include SOD1, which was first identified as the causative gene for familial ALS, as well as the RNA–binding protein FUS, TDP–43 encoded by the TARDBP gene, and the C9ORF72 gene, which has an extended six–base repeat. on the way.
In order to respond to this situation, we are collaborating with five University hospitals in Japan to prepare for the advent of the era of practical gene therapy, and have established the Japan Familial ALS Trial Registry (J–FAST) as a clinical trial ready registry. We will perform rapid screening of SOD1, FUS, TARDBP, and C9ORF72 genes for familial ALS, and add exome and whole genome analysis as necessary. At the same time, by collecting specimens from registered patients, we will also verify unique body fluid and image biomarker candidates, with the goal of searching for pathological surrogate markers. We also plan to collaborate with and compare data with JaCALS, one of the world's largest ALS registries originating from Japan.
