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

Gene Ther. 2000 Aug;7(16):1385-91. doi: 10.1038/sj.gt.3301247.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Animals, Newborn
  • Cytoskeletal Proteins / analysis
  • Cytoskeletal Proteins / deficiency
  • Cytoskeletal Proteins / genetics*
  • Gene Expression
  • Gene Transfer Techniques*
  • Genetic Therapy / methods*
  • Genetic Vectors / administration & dosage*
  • Immunohistochemistry
  • Magnetic Resonance Imaging
  • Membrane Glycoproteins / analysis
  • Membrane Glycoproteins / deficiency
  • Membrane Glycoproteins / genetics*
  • Mice
  • Mice, Inbred mdx
  • Muscle, Skeletal / chemistry
  • Muscle, Skeletal / pathology
  • Muscular Dystrophy, Animal / diagnosis
  • Muscular Dystrophy, Animal / metabolism
  • Muscular Dystrophy, Animal / therapy*
  • Sarcoglycans


  • Cytoskeletal Proteins
  • Membrane Glycoproteins
  • Sarcoglycans