Antisense Oligonucleotide Therapies for Duchenne Muscular Dystrophy

[Speaker] Shin'ichi Takeda:1
1:National Institute of Neuroscience, National Center of Neurology and Psychiatry, Japan

Duchenne muscular dystrophy (DMD) is the most common childhood genetic disease, affecting one among 5,000 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 events (Ann Neurol. 2009;65:667-76). 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 carried an early phase clinical trial of exon 53 skipping of DMD patients, as an investigator-initiated trial in NCNP hospital. Following the excellent results of the early phase trial, the AOs have been chosen as fast track for approval process both in Japan and in US, then phase I/II trial in Japan and phase II trial in US are carrying by either Nippon Shinyaku Co. Ltd. or NS Pharma, Inc.
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