Systemic Treatment of Duchenne Muscular Dystrophy by Antisense Oligomer-Induced Exon Skipping

摘要: Duchenne muscular dystrophy (DMD), caused by nonsense or frame-shift mutations in the dystrophin gene, is a progressive degenerative disease involving all muscles body-wide. Antisense oligomer-mediated exon skipping has recently emerged as an effective approach for restoration of dystrophin. A clinical trial intramuscular delivery antisense oligonucleotide demonstrates efficacy principle DMD patients, providing optimism its application treatment. However, systemic and requires life-long treatment systemically with therapy maintenance expression body-wide muscles, especially cardiac muscle. Unmodified oligomers are able to induce but significant variation between within failure induction Modifying phosphorodiamidate morpholino oligomer (PMO) cell-penetrating peptide polymers greatly improves efficiency leads near normal levels both skeletal improved functions. Clinical trials well under way could represent first realization gene dystrophies.