Microdystrophin gene therapy of @entity296 restores dystrophin-glycoprotein complex and improves sarcolemma integrity in the mdx XXXX heart.

@entity1 @entity712 @entity296 @entity19 @entity1555
BACKGROUND: More than 90% of @entity1555 ( @entity1555 ) @entity1 develop @entity296 , and many die of @entity712 . Despite tremendous progress in skeletal muscle gene therapy, few attempts have been made to treat @entity296 . Microdystrophin genes are shown to correct skeletal muscle pathological lesions in the mdx @entity19 model for @entity1555 . Here, we tested the therapeutic potential of adeno-associated virus (AAV)-mediated microdystrophin gene therapy in the mdx @entity19 heart. METHODS AND RESULTS: AAV was delivered to the newborn mdx @entity19 cardiac cavity. The procedure was rapid and well tolerated. Efficient expression was achieved in the inner and the outer layers of the myocardium. The ubiquitous cytomegalovirus promoter resulted in substantially higher expression than the muscle-specific CK6 promoter. The therapeutic effects of microdystrophin were evaluated at 10 months after infection. Immunostaining demonstrated extensive microdystrophin expression and successful restoration of the dystrophin-glycoprotein complex. Importantly, AAV-mediated microdystrophin expression improved the sarcolemma integrity in the mdx heart. CONCLUSIONS: We established a simple gene transfer method for efficient and persistent transduction of the mdx @entity19 heart. AAV-mediated microdystrophin expression restored the critical dystrophin-glycoprotein complex and improved sarcolemma integrity of the mdx heart. Our results revealed the promise of AAV-microdystrophin gene therapy for @entity296 in @entity1555 .
