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  • Inherited Disease
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Early adenovirus-mediated gene transfer effectively prevents muscular dystrophy in alpha-sarcoglycan-deficient mice

Gene Therapy volume 7, pages 1385–1391 (2000)Cite this article

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 α-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 α-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.

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Acknowledgements

We are indebted to Dr Franck Duclos for generating the Sgca-null mice. We gratefully acknowledge Richard D Anderson and the Gene Therapy Center Vector Core Facility, DK54759 for their support. We thank EPIX Medical/Mallinckrodt Inc. for supplying the contrast agent AngioMark (MS-325) used in this study. We thank members of the Campbell laboratory for fruitful discussions and critical reading of this manuscript. VA is the recipient of a Neuromuscular Disease Research Development Grant from the Muscular Dystrophy Association. VS was supported by a grant from the Deutsche Forschungsgemeinschaft (Str 498/1-1). KMD was supported by The Whitaker Foundation. This work is also funded by a grant from the Muscular Dystrophy Association to KPC. BLD is a fellow of the Roy J Carver Trust. KPC is an Investigator of the Howard Hughes Medical Institute.

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Authors and Affiliations

  1. Department of Physiology and Biophysics and Department of Neurology, Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, IA, USA

    V Allamand, V Straub & K P Campbell

  2. Department of Radiology and Biophysics Research Institute, Medical College of Wisconsin, Milwaukee, WI, USA

    K M Donahue

  3. Department of Anatomy and Cell Biology, University of Iowa College of Medicine, Iowa City, IA, USA

    R L Davisson

  4. Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, IA, USA

    B L Davidson

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  1. V Allamand
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Allamand, V., Donahue, K., Straub, V. et al. Early adenovirus-mediated gene transfer effectively prevents muscular dystrophy in alpha-sarcoglycan-deficient mice. Gene Ther 7, 1385–1391 (2000). https://doi.org/10.1038/sj.gt.3301247

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