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

V ALLAMAND; K. M DONAHUE; V STRAUB; R. L DAVISSON; B. L DAVIDSON; K. P CAMPBELL

doi:10.1038/sj.gt.3301247

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

Journal article

Peer reviewed

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

V ALLAMAND, K. M DONAHUE, V STRAUB, R. L DAVISSON, B. L DAVIDSON and K. P CAMPBELL

Gene therapy, Vol.7(16), pp.1385-1391

2000

DOI: 10.1038/sj.gt.3301247

PMID: 10981665

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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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Title: Subtitle: Early adenovirus-mediated gene transfer effectively prevents muscular dystrophy in alpha-sarcoglycan-deficient mice
Creators: V ALLAMAND - Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, University of Iowa College of Medicine, Iowa City, IA, United States
K. M DONAHUE - Department of Radiology and Biophysics Research Institute, Medical College of Wisconsin, Milwaukee, WI, United States
V STRAUB - Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, University of Iowa College of Medicine, Iowa City, IA, United States
R. L DAVISSON - Department of Anatomy and Cell Biology, University of Iowa College of Medicine, Iowa City, IA, United States
B. L DAVIDSON - Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, IA, United States
K. P CAMPBELL - Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, University of Iowa College of Medicine, Iowa City, IA, United States
Resource Type: Journal article
Publication Details: Gene therapy, Vol.7(16), pp.1385-1391
DOI: 10.1038/sj.gt.3301247
PMID: 10981665
NLM abbreviation: Gene Ther
ISSN: 0969-7128
eISSN: 1476-5462
Publisher: Nature Publishing Group; Basingstoke
Language: English
Date published: 2000
Academic Unit: Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
Record Identifier: 9984020847402771

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