Antisense-mediated exon skipping for Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a severe, progressive muscle wasting disease for which there is currently no cure. The disease is caused by mutations in the DMD gene that completely abolish the function of the protein dystrophin. This thesis focuses on the development of a promising new therapy, so called antisense-mediated exon skipping, that aims to restore the disrupted dystrophin reading frame to allow generation of internally deleted, but partly functional dystrophin proteins, as found in the less severe Becker muscular dystrophy.The thesis describes the DMD gene, the dystrophin protein, diseases associated with mutations in the DMD gene and animal models. It provides an overview of potential therapies for Duchenne muscular dystrophy and describes how antisense-mediated modulation of splicing can be used for other therapeutic and research purposes. Finally it gives a detailed overview of the rationale and the development of the exon skipping therapy for Duchenne muscular dystrophy.