Full functional rescue of a complete muscle (TA) in dystrophic hamsters byadeno-associated virus vector-directed gene therapy

Limb girdle muscular dystrophy (LGMD) 2F is caused by mutations in the delt a-sarcoglycan (SC) gene. Previously, we have shown successful application o f a recombinant adeno-associated virus (AAV) vector for genetic and biochem ical rescue in the Bio14.6 hamster, a homologous animal model for LGMD 2F ( J. Li et al., Gene Ther, 6:74-82, 1999), In this report, we show efficient and long-term delta-SG expression accompanied by nearly complete recovery o f physiological function deficits after a single-dose AAV vector injection into the tibialis anterior muscle of the dystrophic hamsters, AAV vector tr eatment led to more than 97% recovery in muscle strength for both the speci fic twitch forte and the specific tetanic force, when compared to the age-m atched control, Vector treatment also prevented pathological muscle hypertr ophy and resulted in normal muscle weight and size. Finally, vector-treated muscle showed substantial improvement of the histopathology, This is the f irst report of successful functional rescue of an entire muscle after AAV-m ediated gene delivery. This report also demonstrates the feasibility of in vivo gene therapy for LGMD patients by using AAV vectors.