Shinichi Takeda
National Institute of Neuroscience, Japan
Title: On-going exon 53 skipping clinical trial for Duchenne Muscular Dystrophy
Biography
Biography: Shinichi Takeda
Abstract
Duchenne muscular dystrophy (DMD) is the most common childhood genetic disease, affecting one among 3500-5000 newborn boys, causing progressive muscle weakness, heart and respiratory failure and premature death. This disease is caused by the mutations of the DMD gene and there is no cure exists for this disease but a number of promising new molecular therapies are being intensively studied. Exon skipping by antisense oligonucleotides (AOs) is a novel method to restore the reading frame of the mutated DMD gene and rescue dystrophin expression. We have reported that systemic delivery of AOs targeting exon 6 and 8 of the canine DMD gene to CXMDJ, a dystrophin-deficient canine animal model, efficiently restored functional dystrophin proteins at the sarcolemma of these dogs and improved phenotypes of affected dogs without serious adverse effects. We, then, optimized AO sequences, which allow exon 53 skipping of the human DMD gene, together with Nippon Shinyaku Co. Ltd. After numbers of toxicology study of the AOs, NS-065/NCNP-01, we proposed an early phase clinical trial of exon 53 skipping of DMD patients, which was approved by Japanese Pharmaceutical and Medical Devices Agency (PMDA) and the trial, has been successfully carried as an investigator-initiated trial in NCNP hospital. Following the excellent results of the early phase trial, phase I/II trial in Japan and phase II trial in US are carrying by either Nippon Shinyaku Co. Ltd. or NS Pharma, Inc.
