skeletal muscle, calcium dysregulation, gene therapy, muscular dystrophy.
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
improved in AAV9SERCA2a
treated mice. In conclusion, gene targeting of SERCA regulation maybe a potent form of compensatory
therapy for muscular dystrophic disorders.