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Disease Rescue and Increased Lifespan in a Model of Cardiomyopathy and Muscular Dystrophy by Combined AAV Treatments
BACKGROUND: The BIO14.6 hamster is an excellent animal model for inherited cardiomyopathy, because of its lethal and well-documented course, due to a spontaneous deletion of delta-sarcoglycan gene promoter and first exon. The muscle disease is progressive and average lifespan is 11 months, because h...
Autores principales: | , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2660610/ https://www.ncbi.nlm.nih.gov/pubmed/19333401 http://dx.doi.org/10.1371/journal.pone.0005051 |
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author | Vitiello, Carmen Faraso, Stefania Sorrentino, Nicolina Cristina Di Salvo, Giovanni Nusco, Edoardo Nigro, Gerardo Cutillo, Luisa Calabrò, Raffaele Auricchio, Alberto Nigro, Vincenzo |
author_facet | Vitiello, Carmen Faraso, Stefania Sorrentino, Nicolina Cristina Di Salvo, Giovanni Nusco, Edoardo Nigro, Gerardo Cutillo, Luisa Calabrò, Raffaele Auricchio, Alberto Nigro, Vincenzo |
author_sort | Vitiello, Carmen |
collection | PubMed |
description | BACKGROUND: The BIO14.6 hamster is an excellent animal model for inherited cardiomyopathy, because of its lethal and well-documented course, due to a spontaneous deletion of delta-sarcoglycan gene promoter and first exon. The muscle disease is progressive and average lifespan is 11 months, because heart slowly dilates towards heart failure. METHODOLOGY/PRINCIPAL FINDINGS: Based on the ability of adeno-associated viral (AAV) vectors to transduce heart together with skeletal muscle following systemic administration, we delivered human delta-sarcoglycan cDNA into male BIO14.6 hamsters by testing different ages of injection, routes of administration and AAV serotypes. Body-wide restoration of delta-SG expression was associated with functional reconstitution of the sarcoglycan complex and with significant lowering of centralized nuclei and fibrosis in skeletal muscle. Motor ability and cardiac functions were completely rescued. However, BIO14.6 hamsters having less than 70% of fibers recovering sarcoglycan developed cardiomyopathy, even if the total rescued protein was normal. When we used serotype 2/8 in combination with serotype 2/1, lifespan was extended up to 22 months with sustained heart function improvement. CONCLUSIONS/SIGNIFICANCE: Our data support multiple systemic administrations of AAV as a general therapeutic strategy for clinical trials in cardiomyopathies and muscle disorders. |
format | Text |
id | pubmed-2660610 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-26606102009-03-31 Disease Rescue and Increased Lifespan in a Model of Cardiomyopathy and Muscular Dystrophy by Combined AAV Treatments Vitiello, Carmen Faraso, Stefania Sorrentino, Nicolina Cristina Di Salvo, Giovanni Nusco, Edoardo Nigro, Gerardo Cutillo, Luisa Calabrò, Raffaele Auricchio, Alberto Nigro, Vincenzo PLoS One Research Article BACKGROUND: The BIO14.6 hamster is an excellent animal model for inherited cardiomyopathy, because of its lethal and well-documented course, due to a spontaneous deletion of delta-sarcoglycan gene promoter and first exon. The muscle disease is progressive and average lifespan is 11 months, because heart slowly dilates towards heart failure. METHODOLOGY/PRINCIPAL FINDINGS: Based on the ability of adeno-associated viral (AAV) vectors to transduce heart together with skeletal muscle following systemic administration, we delivered human delta-sarcoglycan cDNA into male BIO14.6 hamsters by testing different ages of injection, routes of administration and AAV serotypes. Body-wide restoration of delta-SG expression was associated with functional reconstitution of the sarcoglycan complex and with significant lowering of centralized nuclei and fibrosis in skeletal muscle. Motor ability and cardiac functions were completely rescued. However, BIO14.6 hamsters having less than 70% of fibers recovering sarcoglycan developed cardiomyopathy, even if the total rescued protein was normal. When we used serotype 2/8 in combination with serotype 2/1, lifespan was extended up to 22 months with sustained heart function improvement. CONCLUSIONS/SIGNIFICANCE: Our data support multiple systemic administrations of AAV as a general therapeutic strategy for clinical trials in cardiomyopathies and muscle disorders. Public Library of Science 2009-03-31 /pmc/articles/PMC2660610/ /pubmed/19333401 http://dx.doi.org/10.1371/journal.pone.0005051 Text en Vitiello et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Vitiello, Carmen Faraso, Stefania Sorrentino, Nicolina Cristina Di Salvo, Giovanni Nusco, Edoardo Nigro, Gerardo Cutillo, Luisa Calabrò, Raffaele Auricchio, Alberto Nigro, Vincenzo Disease Rescue and Increased Lifespan in a Model of Cardiomyopathy and Muscular Dystrophy by Combined AAV Treatments |
title | Disease Rescue and Increased Lifespan in a Model of Cardiomyopathy and Muscular Dystrophy by Combined AAV Treatments |
title_full | Disease Rescue and Increased Lifespan in a Model of Cardiomyopathy and Muscular Dystrophy by Combined AAV Treatments |
title_fullStr | Disease Rescue and Increased Lifespan in a Model of Cardiomyopathy and Muscular Dystrophy by Combined AAV Treatments |
title_full_unstemmed | Disease Rescue and Increased Lifespan in a Model of Cardiomyopathy and Muscular Dystrophy by Combined AAV Treatments |
title_short | Disease Rescue and Increased Lifespan in a Model of Cardiomyopathy and Muscular Dystrophy by Combined AAV Treatments |
title_sort | disease rescue and increased lifespan in a model of cardiomyopathy and muscular dystrophy by combined aav treatments |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2660610/ https://www.ncbi.nlm.nih.gov/pubmed/19333401 http://dx.doi.org/10.1371/journal.pone.0005051 |
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