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Co-Administration of Simvastatin Does Not Potentiate the Benefit of Gene Therapy in the mdx Mouse Model for Duchenne Muscular Dystrophy
Duchenne muscular dystrophy (DMD) is the most common and cureless muscle pediatric genetic disease, which is caused by the lack or the drastically reduced expression of dystrophin. Experimental therapeutic approaches for DMD have been mainly focused in recent years on attempts to restore the express...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8878028/ https://www.ncbi.nlm.nih.gov/pubmed/35216132 http://dx.doi.org/10.3390/ijms23042016 |
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author | Bourg, Nathalie Vu Hong, Ai Lostal, William Jaber, Abbass Guerchet, Nicolas Tanniou, Guillaume Bordier, Fanny Bertil-Froidevaux, Emilie Georger, Christophe Daniele, Nathalie Richard, Isabelle Israeli, David |
author_facet | Bourg, Nathalie Vu Hong, Ai Lostal, William Jaber, Abbass Guerchet, Nicolas Tanniou, Guillaume Bordier, Fanny Bertil-Froidevaux, Emilie Georger, Christophe Daniele, Nathalie Richard, Isabelle Israeli, David |
author_sort | Bourg, Nathalie |
collection | PubMed |
description | Duchenne muscular dystrophy (DMD) is the most common and cureless muscle pediatric genetic disease, which is caused by the lack or the drastically reduced expression of dystrophin. Experimental therapeutic approaches for DMD have been mainly focused in recent years on attempts to restore the expression of dystrophin. While significant progress was achieved, the therapeutic benefit of treated patients is still unsatisfactory. Efficiency in gene therapy for DMD is hampered not only by incompletely resolved technical issues, but likely also due to the progressive nature of DMD. It is indeed suspected that some of the secondary pathologies, which are evolving over time in DMD patients, are not fully corrected by the restoration of dystrophin expression. We recently identified perturbations of the mevalonate pathway and of cholesterol metabolism in DMD patients. Taking advantage of the mdx model for DMD, we then demonstrated that some of these perturbations are improved by treatment with the cholesterol-lowering drug, simvastatin. In the present investigation, we tested whether the combination of the restoration of dystrophin expression with simvastatin treatment could have an additive beneficial effect in the mdx model. We confirmed the positive effects of microdystrophin, and of simvastatin, when administrated separately, but detected no additive effect by their combination. Thus, the present study does not support an additive beneficial effect by combining dystrophin restoration with a metabolic normalization by simvastatin. |
format | Online Article Text |
id | pubmed-8878028 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-88780282022-02-26 Co-Administration of Simvastatin Does Not Potentiate the Benefit of Gene Therapy in the mdx Mouse Model for Duchenne Muscular Dystrophy Bourg, Nathalie Vu Hong, Ai Lostal, William Jaber, Abbass Guerchet, Nicolas Tanniou, Guillaume Bordier, Fanny Bertil-Froidevaux, Emilie Georger, Christophe Daniele, Nathalie Richard, Isabelle Israeli, David Int J Mol Sci Article Duchenne muscular dystrophy (DMD) is the most common and cureless muscle pediatric genetic disease, which is caused by the lack or the drastically reduced expression of dystrophin. Experimental therapeutic approaches for DMD have been mainly focused in recent years on attempts to restore the expression of dystrophin. While significant progress was achieved, the therapeutic benefit of treated patients is still unsatisfactory. Efficiency in gene therapy for DMD is hampered not only by incompletely resolved technical issues, but likely also due to the progressive nature of DMD. It is indeed suspected that some of the secondary pathologies, which are evolving over time in DMD patients, are not fully corrected by the restoration of dystrophin expression. We recently identified perturbations of the mevalonate pathway and of cholesterol metabolism in DMD patients. Taking advantage of the mdx model for DMD, we then demonstrated that some of these perturbations are improved by treatment with the cholesterol-lowering drug, simvastatin. In the present investigation, we tested whether the combination of the restoration of dystrophin expression with simvastatin treatment could have an additive beneficial effect in the mdx model. We confirmed the positive effects of microdystrophin, and of simvastatin, when administrated separately, but detected no additive effect by their combination. Thus, the present study does not support an additive beneficial effect by combining dystrophin restoration with a metabolic normalization by simvastatin. MDPI 2022-02-11 /pmc/articles/PMC8878028/ /pubmed/35216132 http://dx.doi.org/10.3390/ijms23042016 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Bourg, Nathalie Vu Hong, Ai Lostal, William Jaber, Abbass Guerchet, Nicolas Tanniou, Guillaume Bordier, Fanny Bertil-Froidevaux, Emilie Georger, Christophe Daniele, Nathalie Richard, Isabelle Israeli, David Co-Administration of Simvastatin Does Not Potentiate the Benefit of Gene Therapy in the mdx Mouse Model for Duchenne Muscular Dystrophy |
title | Co-Administration of Simvastatin Does Not Potentiate the Benefit of Gene Therapy in the mdx Mouse Model for Duchenne Muscular Dystrophy |
title_full | Co-Administration of Simvastatin Does Not Potentiate the Benefit of Gene Therapy in the mdx Mouse Model for Duchenne Muscular Dystrophy |
title_fullStr | Co-Administration of Simvastatin Does Not Potentiate the Benefit of Gene Therapy in the mdx Mouse Model for Duchenne Muscular Dystrophy |
title_full_unstemmed | Co-Administration of Simvastatin Does Not Potentiate the Benefit of Gene Therapy in the mdx Mouse Model for Duchenne Muscular Dystrophy |
title_short | Co-Administration of Simvastatin Does Not Potentiate the Benefit of Gene Therapy in the mdx Mouse Model for Duchenne Muscular Dystrophy |
title_sort | co-administration of simvastatin does not potentiate the benefit of gene therapy in the mdx mouse model for duchenne muscular dystrophy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8878028/ https://www.ncbi.nlm.nih.gov/pubmed/35216132 http://dx.doi.org/10.3390/ijms23042016 |
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