Journal article

Microutrophin delivery through rAAV6 increases lifespan and improves muscle function in dystrophic dystrophin/utrophin-deficient mice

Guy L Odom, Paul Gregorevic, James M Allen, Eric Finn, Jeffrey S Chamberlain

MOLECULAR THERAPY | CELL PRESS | Published : 2008

Abstract

Duchenne muscular dystrophy (DMD), the most prevalent lethal genetic disorder in children, is caused by mutations in the 2.2-MB dystrophin gene. Absence of dystrophin and the dystrophin-glycoprotein complex (DGC) from the sarcolemma leads to severe muscle wasting and eventual respiratory and/or cardiac failure. There is presently no effective therapy for DMD. Several lines of evidence have suggested that methods to increase expression of utrophin, a dystrophin paralog, show promise as a treatment for DMD. Adeno-associated viral (AAV) vectors are a promising vehicle for gene transfer to muscle, but microutrophin transgenes small enough to be carried by AAV have not been tested for function. I..

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University of Melbourne Researchers

Grants

Awarded by National Institutes of Health


Awarded by National Institutes of Health National Research Service Award


Awarded by NATIONAL HEART, LUNG, AND BLOOD INSTITUTE


Awarded by NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES


Awarded by NATIONAL INSTITUTE ON AGING


Funding Acknowledgements

We are grateful to Leonard Meuse for animal husbandry, Caitlyn Doremus for rAAV vector production assistance, and Miki Haraguchi for histopathological support. We thank Stan Froehner for providing the antibodies used in the study, and Marvin Adams of the University of Washington for his critical reading of this manuscript. We also thank Greg Martin at the Keck Imaging Center, University of Washington, for assistance with confocal microscopy, and Chamberlain laboratory members for critically reviewing the manuscript. This work was supported by grants from the National Institutes of Health (R37AR40864) and the Muscular Dystrophy Association (to J.S.C.). G.L.O. was supported by a National Institutes of Health National Research Service Award (T32 HL07828). P. G. was supported by a Development Grant from the Muscular Dystrophy Association.