Document Detail

AAV-microdystrophin therapy improves cardiac performance in aged female mdx mice.
MedLine Citation:
PMID:  21811246     Owner:  NLM     Status:  MEDLINE    
Dystrophin deficiency leads to lethal dilated Duchenne cardiomyopathy. A promising therapy is to deliver a highly abbreviated microdystrophin gene to the heart using adeno-associated virus (AAV). Microdystrophin has been shown to mitigate dystrophin-deficient skeletal muscle disease. However, it is not clear whether microdystrophin is equally effective in treating Duchenne cardiomyopathy. To evaluate microdystrophin therapy in the heart, we injected 5 × 10(12) viral genome particles/mouse of AAV-9 ΔR4-23/ΔC microdystrophin vector via tail vein to ~16-20-month-old (average 18.7-month-old) female mdx mice, a manifesting model of Duchenne cardiomyopathy. Cardiac transduction and heart function were examined at 2-8 months after gene transfer. We observed robust myocardial microdystrophin expression. Electrocardiography (ECG) and left ventricular catheter hemodynamic assays also revealed significant improvement. Furthermore, AAV-microdystrophin therapy prevented dobutamine-stress induced acute cardiac death. We demonstrate for the first time that AAV microdystrophin therapy significantly ameliorates functional deficiency in a phenotypic model of Duchenne cardiomyopathy. Our results support further exploration of microdystrophin therapy to treat Duchenne cardiomyopathy.
Brian Bostick; Jin-Hong Shin; Yongping Yue; Dongsheng Duan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-08-02
Journal Detail:
Title:  Molecular therapy : the journal of the American Society of Gene Therapy     Volume:  19     ISSN:  1525-0024     ISO Abbreviation:  Mol. Ther.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-03     Completed Date:  2012-02-03     Revised Date:  2014-09-19    
Medline Journal Info:
Nlm Unique ID:  100890581     Medline TA:  Mol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1826-32     Citation Subset:  IM    
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MeSH Terms
Aging / physiology*
Dependovirus / genetics*
Dobutamine / adverse effects
Dystrophin / genetics,  therapeutic use*
Genetic Vectors
Heart Function Tests*
Mice, Inbred mdx
Transduction, Genetic
Grant Support
Reg. No./Substance:
0/Dystrophin; 3S12J47372/Dobutamine

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