Open AccessAdeno-Associated Virus Serotype-9 Microdystrophin Gene Therapy Ameliorates Electrocardiographic Abnormalities in mdx Mice
Author(s) -
Brian Bostick,
Yongping Yue,
Yi Lai,
Chun Long,
Dejia Li,
Dongsheng Duan
Publication year - 2008
Publication title -
human gene therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.633
H-Index - 149
eISSN - 1557-7422
pISSN - 1043-0342
DOI - 10.1089/hum.2008.058
Subject(s) - genetic enhancement , duchenne muscular dystrophy , adeno associated virus , mdx mouse , gene delivery , medicine , muscular dystrophy , qt interval , serotype , dystrophin , viral vector , skeletal muscle , cardiomyopathy , cardiology , virology , vector (molecular biology) , gene , heart failure , biology , genetics , recombinant dna
Adeno-associated virus (AAV)-mediated microdystrophin gene therapy holds great promise for treating Duchenne muscular dystrophy (DMD). Previous studies have revealed excellent skeletal muscle protection. Cardiac muscle is also compromised in DMD patients. Here we show that a single intravenous injection of AAV serotype-9 (AAV-9) microdystrophin vector efficiently transduced the entire heart in neonatal mdx mice, a dystrophin-deficient mouse DMD model. Furthermore, microdystrophin therapy normalized the heart rate, PR interval, and QT interval. The cardiomyopathy index was also significantly improved in treated mdx mice. Our study demonstrates for the first time that AAV microdystrophin gene therapy can ameliorate the electrocardiographic abnormalities in a mouse model for DMD.