Micro-utrophin improves cardiac and skeletal muscle function of severely affected D2/mdx mice
| Autor: | Kennedy, T, Guiraud, S, Edwards, B, Squire, S, Moir, L, Babbs, A, Odom, G, Golebiowski, D, Schneider, J, Chamberlain, J, Davies, K |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: | |
| Zdroj: | Molecular Therapy: Methods & Clinical Development, Vol 11, Iss, Pp 92-105 (2018) Molecular Therapy. Methods & Clinical Development |
| Popis: | Duchenne muscular dystrophy (DMD) is an X-linked muscle-wasting disease caused by mutations in the dystrophin gene. DMD boys are wheelchair-bound around 12 years and generally survive into their twenties. There is currently no effective treatment except palliative care, although personalized treatments such as exon skipping, stop codon read-through, and viral-based gene therapies are making progress. Patients present with skeletal muscle pathology, but most also show cardiomyopathy by the age of 10. A systemic therapeutic approach is needed that treats the heart and skeletal muscle defects in all patients. The dystrophin-related protein utrophin has been shown to compensate for the lack of dystrophin in the mildly affected BL10/mdx mouse. The purpose of this investigation was to demonstrate that AAV9-mediated micro-utrophin transgene delivery can not only functionally replace dystrophin in the heart, but also attenuate the skeletal muscle phenotype in severely affected D2/mdx mice. The data presented here show that utrophin can indeed alleviate the pathology in skeletal and cardiac muscle in D2/mdx mice. These results endorse the view that utrophin modulation has the potential to increase the quality life of all DMD patients whatever their mutation. Keywords: Duchenne, utrophin, AAV, D2/mdx, cardiomyopathy, cardiac cine-MRI |
| Databáze: | OpenAIRE |
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