筋萎縮性側索硬化症の病態解明・治療法開発への試み

I graduated from Tokushima University in １９９５ and trained at Hiroshima University and Sumitomo Hospital. In２０００, Professor Ryuji Kaji was appointed as the first professor of the Department of Neurology, Tokushima University. In ２００１, I graduated from Hiroshima University Graduate School and returned to Tokushima University. At the Department of Neurology, Tokushima University, we have been investigating natural history, neurophysiology including neuromuscular sonology, MRI, liquid biomarkers, genes, neuropathology, iPS cells, and new treatments as research on amyotrophic lateral sclerosis（ALS）（Tokushima ALS Research）. We have examined the effect of methylcobalamin on ALS as a new therapeutic candidate. A phase Ⅲ study, Japanese Early-stage Trial of ultra-high dose methylcobalamin for ALS（JETALS）, was carried out. Patients with ALS diagnosed within１year of onset by the updated Awaji criteria were initially enrolled. Of those, patients fulfilling the following criteria after１２‐week observation were eligible for randomization :１- or ２-point decrease in ALS Functional Rating Scale Revised （ALSFRS-R）total score, a percent forced vital capacity over ６０％, no history of noninvasive respiratory support and tracheostomy, and being ambulant. Methylcobalamin ５０ mg or placebo was intramuscularly injected twice weekly for １６ weeks. The primary endpoint was change in ALSFRS-R total score from baseline to week １６. As a result, the least-squares mean difference in ALSFRS-R total score at week １６ of the randomized period was １．９７ points greater with methylcobalamin than placebo. The incidence of adverse events was similar between the two groups.
In the future, we plan to work on elucidating the pathophysiology of ALS, developing more powerful treatments for ALS, and dealing with non-motor symptoms of ALS.