Translational research on DMD in Japan: From mice to exploratory investigator-initiated clinical trial in human

Abstract

Currently, antisense oligonucleotides (AONs)-mediated exon skipping therapy is the most promising therapy for Duchenne muscular dystrophy. We performed preclinical studies using dystrophic mdx52 mice and CXMDJ dystrophic dogs to obtain proof of concept of AONs-mediated exon skipping therapy. Then, Japan participated in the worldwide clinical trials of drisapersen (Phase III). Finally, we developed a new AON targeting exon 53 in collaboration with Nippon Shinyaku Co., Ltd. in Japan and started an investigator-initiated clinical study at the National Center Hospital of NCNP (Phase I). This early phase exploratory study is the first clinical trial of an AON developed in Japan and a good example of translational research for treatment of DMD in Japan. In this chapter, we summarize the long development of the drug and discuss the future direction of splicing therapy for DMD.