Basic principles and clinical applications in therapeutic oligonucleotides targeting neuromuscular diseases

Abstract

Therapeutic oligonucleotide is one of most promising modalities for molecular–targeted therapy as well as antibody therapy and gene therapy. This nucleic acid drugs bind to targeted molecules, mainly RNA, directly and include antisense nucleotides and small interfering RNA. Recent progress in basic and clinical research of therapeutic oligonucleotides has been remarkable, especially for treatment of intractable neuromuscular diseases. In 2016, nusinersen was approved by the FDA as the first drug which enables disease–modifying and improving clinical outcome of spinal muscular atrophy. In addition, in 2020, viltolarsen was approved as a first antisense oligonucleotide which has been developed in Japan. Patisiran for TTR–type FAP was approved in 2018 as the first siRNA drug. In 2022, Vutrisiran was newly approved by the FDA and approved to date in Japan. Here, we review molecular mechanism and progress of clinical development of nucleic acid medicines targeting neuromuscular disease which have been accepted in Japan for clinical application.