[PS17] Parallel Session 17: Neuromuscular Disorder

[PS17-3A-K] Fundamental Treatments of Duchenne muscular dystrophy

^○Masafumi MATSUO (Faculty of Rehabilitation, Kobe Gakuin University, Emeritus Professor, Kobe University, Japan)

Duchenne muscular dystrophy (DMD) is the most common inherited muscular disease with a worldwide incidence of 1 in 3500 male boys. DMD is characterized by muscle dystrophin deficiency caused by mutations in the dystrophin gene and is a lethal progressive muscle wasting disease. The affected individuals show muscle weakness at the age of 3 to 5 years and are wheelchair bound by the age of 12years. They succumb to cardiac or respiratory failure in the late 20s or 30s. Establishment of treatment has long been awaited. Many kinds of strategies from gene replacement therapy to anti-inflammatory agents have been proposed as treatments for DMD. Especially, a fundamental treatment to express dystrophin has long been the ultimate goal for DMD studies. Recently two compounds aiming to express dystrophin acquired the official marketing approval. One is Ataluren® that induces the ribosomal read through, thereby enabling dystrophin production from the nonsense-encoding mRNA. The other one is Eteprilsen® that induces skipping of dystrophin exon 51 during splicing, thereby enabling internally deleted dystrophin production. Both of these are mutation specific treatments. In japan we have developed an antisense ENA(ethylene bridged nucleic acid)/RNA oligonucleotide that induces dystrophin exon 45 skipping. Currently, ENA/RNA is under a phaseⅠ/Ⅱclinical trial. In this keynote speech fundamental treatments of DMD are reviewed focusing on development of antisense-mediated exon skipping therapy.

Reference
Matsuo M. et al. Contributions of Japanese patients to development of antisense therapy for DMD. Brain Dev. 2016;38:4-9.