X. Xiao et al., Full functional rescue of a complete muscle (TA) in dystrophic hamsters byadeno-associated virus vector-directed gene therapy, J VIROLOGY, 74(3), 2000, pp. 1436-1442
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.