AAV9-mediated gene transfer of desmin ameliorates cardiomyopathy in desmin-deficient mice
Mutations of the human desmin (DES) gene cause autosomal dominant and recessive myopathies affecting skeletal and cardiac muscle tissue. Desmin knockout mice (DES-KO), which develop progressive myopathy and cardiomyopathy, mirror rare human recessive desminopathies in which mutations on both DES all...
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| Main Authors: | , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
August 2016
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| In: |
Gene therapy
Year: 2016, Volume: 23, Issue: 8, Pages: 673-679 |
| ISSN: | 1476-5462 |
| DOI: | 10.1038/gt.2016.40 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1038/gt.2016.40 Verlag, Volltext: https://www.nature.com/articles/gt201640 
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| Author Notes: | M.B. Heckmann, R. Bauer, A. Jungmann, L. Winter, K. Rapti, K.-H. Strucksberg, C.S. Clemen, Z. Li, R. Schröder, H.A. Katus and O.J. Müller |
| Summary: | Mutations of the human desmin (DES) gene cause autosomal dominant and recessive myopathies affecting skeletal and cardiac muscle tissue. Desmin knockout mice (DES-KO), which develop progressive myopathy and cardiomyopathy, mirror rare human recessive desminopathies in which mutations on both DES alleles lead to a complete ablation of desmin protein expression. Here, we investigated whether an adeno-associated virus-mediated gene transfer of wild-type desmin cDNA (AAV-DES) attenuates cardiomyopathy in these mice. Our approach leads to a partial reconstitution of desmin protein expression and the de novo formation of the extrasarcomeric desmin-syncoilin network in cardiomyocytes of treated animals. This finding was accompanied by reduced fibrosis and heart weights and improved systolic left-ventricular function when compared with control vector-treated DES-KO mice. Since the re-expression of desmin protein in cardiomyocytes of DES-KO mice restores the extrasarcomeric desmin-syncoilin cytoskeleton, attenuates the degree of cardiac hypertrophy and fibrosis, and improves contractile function, AAV-mediated desmin gene transfer may be a novel and promising therapeutic approach for patients with cardiomyopathy due to the complete lack of desmin protein expression. |
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| Item Description: | Gesehen am 13.11.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1476-5462 |
| DOI: | 10.1038/gt.2016.40 |