2016 Volume 33 Issue 2 Pages 83-87
Although recent advance in molecular biology have provided increasing insights into the pathophysiology of neurodegenerative diseases, there is no established disease–modifying therapy for which the efficacy has been verified in clinical trials.
Spinal and bulbar muscular atrophy (SBMA) is an adult–onset neuromuscular disease caused by the expansion of a trinucleotide CAG repeat in the androgen receptor (AR) gene. The ligand–dependent nuclear accumulation of pathogenic AR protein is central to the pathogenesis. Leuprorelin, a luteinizing hormone–releasing hormone (LHRH) analogue that suppresses testosterone production from testis, inhibits toxic accumulation of pathogenic AR, thereby mitigating histopathological and behavioral impairments in a mouse model of SBMA. A randomized placebo–controlled multi–centric phase 3 clinical trial showed an effect of the drug on motor functions, furthermore there was a significant improvement of swallowing function in a subgroup of patients whose disease duration was less than 10 years. In addition, a long–term follow–up study compared with natural history group of patients revealed that the progression of motor dysfunction and occurrence of pneumoniae due to swallowing dysfunction were very much diminished with leuprorelin treatment.
Amyotrophic lateral sclerosis (ALS) is an adult–onset neurodegenerative disease characterized by progressive upper and lower motor neuron loss, which leads to limb and bulbar paralysis and respiratory failure. We constructed a multicentre registration and follow–up system called the Japanese Consortium for Amyotrophic Lateral Sclerosis research (JaCALS). Using this registry system, several investigations have been performed. We hope that our report will be helpful for clinicians who want to provide medical, social, and nursing care to patients with ALS with proper timing, and to researchers as they plan clinical trials for ALS.
