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

Limb-girdle muscular dystrophy type 2D (LGMD 2D) is the most common cause o f 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-mediat ed gene transfer of human alpha-sarcoglycan. Here we report that a single i ntramuscular injection of a first generation adenovirus into the skeletal m uscle of neonate mice led to sustained expression of alpha-sarcoglycan at t he sarcolemma of transduced myofibers for at least 7 months. The morphology of transduced muscles was consequently pre-served. In addition, we have us ed contrast agent-enhanced magnetic resonance imaging (MRI) to investigate sarcolemmal integrity in adenovirus-injected animals and have thereby demon strated maintenance of sarcolemmal function. In conclusion, we provide evid ence that early virus-mediated gene transfer of a sarcoglycan protein const itutes a promising therapeutic strategy for LGMDs and that the benefits of this approach can easily and effectively be monitored by noninvasive method ologies such as MRI.