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• W2046113375 abstract "Duchenne muscular dystrophy (DMD) is the most common inherited lethal muscle degenerative disease. Currently there is no cure. Highly abbreviated microdystrophin cDNAs were developed recently for adeno-associated virus (AAV)-mediated DMD gene therapy. Among these, a C-terminal-truncated DeltaR4-R23/DeltaC microgene (DeltaR4/DeltaC) has been considered as a very promising therapeutic candidate gene. In this study, we packaged a CMV.DeltaR4/DeltaC cassette in AAV-5 and evaluated the transduction and muscle contractile profiles in the extensor digitorum longus muscles of young (7-week-old) and adult (9-month-old) mdx mice. At approximately 3 months post-gene transfer, 50-60% of the total myofibers were transduced in young mdx muscle and the percentage of centrally nucleated myofibers was reduced from approximately 70% in untreated mdx muscle to approximately 22% in microdystrophin-treated muscle. Importantly, this level of transduction protected mdx muscle from eccentric contraction-induced damage. In contrast, adult mdx muscle was more resistant to AAV-5 transduction, as only approximately 30% of the myofibers were transduced at 3 months postinfection. This transduction yielded marginal protection against eccentric contraction-induced injury. The extent of central nucleation was also more difficult to reverse in adult mdx muscle (from approximately 83% in untreated to approximately 58% in treated). Finally, we determined that the DeltaR4/DeltaC microdystrophin did not significantly alter the expression pattern of the endogenous full-length dystrophin in normal muscle. Neither did it have any adverse effects on normal muscle morphology or contractility. Taken together, our results suggest that AAV-mediated DeltaR4/DeltaC microdystrophin expression represents a promising approach to rescue muscular dystrophy in young mdx skeletal muscle." @default.
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• W2046113375 date "2005-02-01" @default.
• W2046113375 modified "2023-10-18" @default.
• W2046113375 title "Adeno-Associated virus-mediated microdystrophin expression protects young mdx muscle from contraction-induced injury" @default.
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• W2046113375 doi "https://doi.org/10.1016/j.ymthe.2004.09.013" @default.
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