Nonsense readthrough therapy for duchenne muscular dystrophy

Abstract

Duchenne muscular dystrophy (DMD) is the most common form of inherited muscle disease and is characterized by progressive muscle wasting ultimately resulting in death of the patients in their twenties. DMD is characterized by a deficiency of the muscle dystrophin as a result of mutations in the dystrophin gene. Currently, no effective treatment for DMD is available. Promising molecular therapies which are mutation specific have been developed. Induction of the readthrough of nonsense mutations is expected to produce dystrophin in DMD patients with nonsense mutations, which are detected in 19% of DMD cases. Clinical effectiveness of gentamicin and PTC124 have been suggested. We have demonstrated that arbekacin-mediated readthrough can substantially ameliorate muscular dystrophy. We already have begun the clinical trial of the nonsense mutation readthrough therapy using arbekacin. We hope that this molecular therapy will contribute towards the treatment for DMD.