2018 Volume 35 Issue 4 Pages 488-493
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 the SOD1 gene in 1993 as the causative gene, more than 20 genes, such as FUS, the second most frequent Japanese, and C9ORF72, the most frequent in Europe and America, have been clarified. Our research group developed an ALS rat model with SOD1 mutation, which recapitulates the motor neuron pathology found in human ALS cases. A continuous administration of hepatocyte growth factor (HGF) using the osmotic pump into the intrathecal cavity of ALS rat model showed a significant prolongation of disease duration at 63%. In 2014, the phase I study of intrathecal administration of HGF for patients with ALS at Tohoku University Hospital was conducted to confirm safety and pharmacokinetics. Currently, phase II clinical trials are being conducted with the aim of obtaining a proof of concept. In the current placebo–controlled double–blind study, the total number of cases is 48 at the Tohoku University and Osaka University. The primary endpoint is the reduction in the ALSFRS–R score evaluated for 24 weeks. On the basis of a 3–month observation period, patients with similar progression are involved. We have mentioned the candidate therapeutic targets that have been clarified through rodent models, such as pathological analysis of nerve axon in the early stage of ALS mouse model and abnormalities in immune mechanism of C9ORF72–deficient mice.
