Exon skipping with morpholino oligomers: new treatment option for cardiomyopathy in Duchenne muscular dystrophy?

Abstract

The dystrophin gene encodes an essential component of the transmembrane dystrophin–glycoprotein complex (DGC), which plays a critical role in maintaining membrane stability in cardiac and skeletal muscles.1 Defects in dystrophin destabilize the entire complex, which results in an abnormal susceptibility to sarcolemmal injury in response to contractile stress.2 Mutations that cause slight sequence alterations or loss of internal exons but conserve the reading frame result in Becker muscular dystrophy with a mild phenotype. Complete absence of dystrophin causes Duchenne muscular dystrophy (DMD), a X-chromosomal, fatal, and inherited muscle disease. Affected boys show progressive muscle weakness, leading to early immobility, respiratory failure, and markedly reduced life expectancy. Cardiomyopathy is an almost invariable complication and a frequent cause of death in these patients.3 As a consequence of improvements in overall management for DMD patients, survival has steadily improved. In older patients, however, there is an increasing proportion of patients experiencing premature death due to ventricular dysfunction. Therefore, appropriate treatment strategies to target the cardiomyopathy become more and more crucial to reduce mortality. Thus far, there is no established curative approach to DMD. However, there now seems to be hope since the identification of the molecular basis of this inherited disease has translated into recent therapeutic principles to … *Corresponding author. Tel: +49 6221 5639401; fax: +49 6221 564866. E-mail address : oliver.mueller{at}med.uni-heidelberg.de