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Improvement of cardiac fibrosis in dystrophic mice by rAAV9-mediated microdystrophin transduction
- Source :
- Gene therapy. 18(9)
- Publication Year :
- 2011
-
Abstract
- Duchenne muscular dystrophy (DMD) is the most common form of the progressive muscular dystrophies characterized by defects of the dystrophin gene. Although primarily characterized by degeneration of the limb muscles, cardiomyopathy is a major cause of death. Therefore, the development of curative modalities such as gene therapy is imperative. We evaluated the cardiomyopathic features of mdx mice to observe improvements in response to intravenous administration of recombinant adeno-associated virus (AAV) type 9 encoding microdystrophin. The myocardium was extensively transduced with microdystrophin to significantly prevent the development of fibrosis, and expression persisted for the duration of the study. Intraventricular conduction patterns, such as the QRS complex duration and S/R ratio in electrocardiography, were also corrected, indicating that the transduced microdystrophin has a protective effect on the dystrophin-deficient myocardium. Furthermore, BNP and ANP levels were reduced to normal, suggesting the absence of cardiac dysfunction. In aged mice, prevention of ectopic beats as well as echocardiographic amelioration was also demonstrated with improved exercise performance. These findings indicate that AAV-mediated cardiac transduction with microdystrophin might be a promising therapeutic strategy for the treatment of dystrophin-deficient cardiomyopathy.
- Subjects :
- medicine.medical_specialty
Aging
Cardiac fibrosis
Genetic enhancement
Duchenne muscular dystrophy
Genetic Vectors
Cardiomyopathy
Gene delivery
Dystrophin
Mice
Fibrosis
Transduction, Genetic
Internal medicine
Genetics
Medicine
Animals
Humans
Transgenes
Molecular Biology
Cause of death
medicine.diagnostic_test
business.industry
Myocardium
Genetic Therapy
Dependovirus
medicine.disease
Virology
Muscular Dystrophy, Duchenne
cardiovascular system
Cardiology
Mice, Inbred mdx
Molecular Medicine
business
Cardiomyopathies
Electrocardiography
Subjects
Details
- ISSN :
- 14765462
- Volume :
- 18
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Gene therapy
- Accession number :
- edsair.doi.dedup.....f2a0f8f72cf05b5d29883d9af2e7b448