| AAV-microdystrophin therapy improves cardiac performance in aged female mdx mice. | |
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MedLine Citation:
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PMID: 21811246 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Brian Bostick; Jin-Hong Shin; Yongping Yue; Dongsheng Duan |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-08-02 |
Journal Detail:
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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:
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Created Date: 2011-10-03 Completed Date: 2012-02-03 Revised Date: 2013-02-08 |
Medline Journal Info:
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Nlm Unique ID: 100890581 Medline TA: Mol Ther Country: United States |
Other Details:
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Languages: eng Pagination: 1826-32 Citation Subset: IM |
Affiliation:
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Department of Molecular Microbiology and Immunology, School of Medicine, The University of Missouri, Columbia, Missouri 65212, USA. duand@missouri.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aging
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physiology* Animals Dependovirus / genetics* Dobutamine / adverse effects Dystrophin / genetics, therapeutic use* Electrocardiography Female Genetic Vectors Heart Function Tests* Hemodynamics Mice Mice, Inbred mdx Transduction, Genetic |
| Grant Support | |
ID/Acronym/Agency:
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HL-91883/HL/NHLBI NIH HHS; R01 HL091883-03/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Dystrophin; 34368-04-2/Dobutamine |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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