Conference Publication Details
Mandatory Fields
Bahri, O.A.,McCarthy,S.,Gao,G. and McCullagh, K.J.A.
Cell Symposia: Exercise Metabolism
Adenoassociated viral delivery of serca2a into mdx hindlimb skeletal muscles
2015
July
Published
1
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Optional Fields
skeletal muscle, calcium dysregulation, gene therapy, muscular dystrophy.
Cell
0204
Amsterdam, The Netherlands
12-JUL-15
14-JUL-15
Muscle degenerative disorders are associated with calcium dysregulation. Transgenic overexpression of sarco/endoplasmic reticulum Ca2+ATPase (SERCA) in muscular dystrophic mice was shown to dramatically reduce the dystrophic phenotype and improve muscle function, although the mechanism is unknown. We examined the effect of viral over expression of the (SERCA2a) gene in hindlimb muscles of the mdx mouse model of Duchenne Muscular Dystrophy. Morphological indexes of the dystrophic phenotype were improved in the mdx treated mice compared to controls including a decrease in both fibre size heterogeneity and central nucleated fibres, 6 weeks after a single muscle injection. SERCA allosteric inhibitors phospholamban, sarcolipin, and myoregulin were altered in dystrophic muscle and SERCA treated muscles respectively. Hindlimb gripstrength was improved in AAV9SERCA2a versus AA9GFP treated mice. In conclusion, gene targeting of SERCA regulation maybe a potent form of compensatory therapy for muscular dystrophic disorders.
Health Research Board Ireland & Saudi Arabian Government
Grant Details
RHR895
Publication Themes
Biomedical Science and Engineering