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Early adenovirus-mediated gene transfer effectively prevents muscular dystrophy in alpha-sarcoglycan-deficient mice. Gene Ther 2000 Aug;7(16):1385-91

Date

09/12/2000

Pubmed ID

10981665

DOI

10.1038/sj.gt.3301247

Abstract

Limb-girdle muscular dystrophy type 2D (LGMD 2D) is the most common cause of LGMD with a sarcoglycan defect. We recently engineered a murine model for this progressive disease and we investigated the possibility of preventing the development of muscular dystrophy in these animals by adenovirus-mediated gene transfer of human alpha-sarcoglycan. Here we report that a single intramuscular injection of a first generation adenovirus into the skeletal muscle of neonate mice led to sustained expression of alpha-sarcoglycan at the sarcolemma of transduced myofibers for at least 7 months. The morphology of transduced muscles was consequently preserved. In addition, we have used contrast agent-enhanced magnetic resonance imaging (MRI) to investigate sarcolemmal integrity in adenovirus-injected animals and have thereby demonstrated maintenance of sarcolemmal function. In conclusion, we provide evidence that early virus-mediated gene transfer of a sarcoglycan protein constitutes a promising therapeutic strategy for LGMDs and that the benefits of this approach can easily and effectively be monitored by noninvasive methodologies such as MRI.

Author List

Allamand V, Donahue KM, Straub V, Davisson RL, Davidson BL, Campbell KP

Author

Kathleen M. Schmainda PhD Professor in the Biophysics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adenoviridae
Animals
Animals, Newborn
Cytoskeletal Proteins
Gene Expression
Gene Transfer Techniques
Genetic Therapy
Genetic Vectors
Immunohistochemistry
Magnetic Resonance Imaging
Membrane Glycoproteins
Mice
Mice, Inbred mdx
Muscle, Skeletal
Muscular Dystrophy, Animal
Sarcoglycans