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Human Gene Therapy
Although the precise pathophysiological mechanism of muscle damage in dystrophin-deficient muscle remains disputed, calcium appears to be a critical mediator of the dystrophic process. Duchenne muscular dystrophy patients and mouse models of dystrophin deficiency exhibit extensive abnormalities of calcium homeostasis, which we hypothesized would be mitigated by increased expression of the sarcoplasmic reticulum calcium pump. Neonatal adeno-associated virus gene transfer of sarcoplasmic reticulum ATPase 1a to the mdx diaphragm decreased centrally located nuclei and resulted in reduced susceptibility to eccentric contraction-induced damage at 6 months of age. As the diaphragm is the mouse muscle most representative of human disease, these results provide impetus for further investigation of therapeutic strategies aimed at enhanced cytosolic calcium removal.
This is a copy of an article published in the Human Gene Therapy © 2010 [copyright Mary Ann Liebert, Inc.]; Human Gene Therapy is available online at: http://www.liebertonline.com.
Morine, K. J., Sleeper, M. M., Barton, E. R., & Sweeney, H. L. (2010). Overexpression of SERCA1a in the mdx Diaphragm Reduces Susceptibility to Contraction-Induced Damage. Human Gene Therapy, 21 (12), 1735-1739. http://dx.doi.org/10.1089/hum.2010.077
Date Posted: 24 July 2013
This document has been peer reviewed.