Official websites use. Share sensitive information only on official, secure websites. Correspondence to: Dr. Kildare, Ireland Tel. The disintegration of the dystrophin-glycoprotein complex represents the initial pathobiochemical insult in Duchenne muscular dystrophy.
However, secondary changes in signalling, energy metabolism and ion homeostasis are probably the main factors that eventually cause progressive muscle wasting. Thus, for the proper evaluation of novel therapeutic approaches, it is essential to analyse the reversal of both primary and secondary abnormalities in treated muscles.
Antisense oligomer-mediated exon skipping promises functional restoration of the primary deficiency in dystrophin. In this study, an established phosphorodiamidate morpholino oligomer coupled to a cell-penetrating peptide was employed for the specific removal of exon 23 in the mutated mouse dystrophin gene transcript. Using DIGE analysis, we could show the reversal of secondary pathobiochemical abnormalities in the dystrophic diaphragm following exon skipping.
This clearly establishes the exon-skipping approach as a realistic treatment strategy for diminishing diverse downstream alterations in dystrophinopathy. Keywords: antisense oligomer, DIGE, exon skipping, mdx , muscular dystrophy.
Duchenne muscular dystrophy DMD is a lethal genetic disease of childhood that severely affects the integrity of muscle fibres [ 1 ]. Dystrophinopathies are characterized by primary abnormalities in the Dp isoform of the membrane cytoskeletal protein dystrophin [ 2 ]. Various strategies for the therapy of dystrophinopathies and related muscular disorders have been evaluated, including biomedical interventions based on the down-regulation of myostatin or utrophin substitution, pharmacological treatments, myoblast transfer, stem cell therapy and gene transfer approaches [ 3 - 10 ].
