Translational research for neuromuscular diseases

Abstract

Muscular dystrophy is genetic muscle diseases following with progressive muscle weakness. Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy, and the gene responsible for DMD was identified by using a positional cloning technique in 1986. Since the discovery of DMD gene, our understanding on the structure of dystrophin protein, dystrophin–associated protein complexes or pathogenesis has dramatically improved. These knowledges obtained by DMD research have provided the basis for potential therapies, and have particularly contributed to the development of therapies targeting mRNA and genomic DNA. Exon–skipping therapy using antisense nucleic acid (AON) targeting pre–mRNA has been successfully correct out–of–frame mRNAs to produce in–frame transcripts by removing an exon during splicing, with the restoration of functionally preserved dystrophin protein, and is currently approved in US and Japan. Recent advances in genetic analysis techniques including next–generation sequencing (NGS) have made it possible to identify many causative genes and proteins, to diagnose multiple types of muscular dystrophies and to develop potential therapies. In addition to DMD, novel technologies have contributed to the elucidation of pathogenesis in several muscular diseases including myotonic dystrophy (DM), Fukuyama congenital muscular dystrophy (FCMD), GNE myopathy and MELAS, paving the way for clinical research and drug discovery. We hope that further innovation will encourage the progress of basic research, and contribute to breakthrough for the development of therapies for non–curable diseases.