[Therapeutic development in myotonic dystrophy]

Myotonic dystrophy (DM), the commonest form of muscular dystrophy in adults, is a multisystem disease caused by repeat expansions located in untranslated regions of the affected genes. Its pathogenesis results from expression of RNAs with these expanded repeats, which causes sequestration of splicing factors and thus series of splicing misregulation. An increased understanding of the disease mechanism has accelerated the development of therapeutic strategies, including correction of individual missplicing by antisense oligonucleotides (ASOs), ASO- or small molecule-mediated neutralization of the RNA toxicity by preventing sequestration of splicing factors, degradation of the toxic RNA by ASOs, and stabilization of the expanded repeats. ASOs targeting the toxic RNA have exhibited promising results in animal models, and a clinical trial has recently been launched. With the advent of clinical trials, we are confronting several challenges. As with other rare diseases, we must identify eligible patients. It may be more important in Japan to establish a standardized best practice management of currently available approaches (e.g., pacemaker use) followed by nationwide dissemination. The national DM registry, about to be launched shortly, might be a promising tool to overcome these issues and lead to improved management of DM.