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...
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2022-02-01
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| Series: | International Journal of Molecular Sciences |
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| author | Nathalie Bourg Ai Vu Hong William Lostal Abbass Jaber Nicolas Guerchet Guillaume Tanniou Fanny Bordier Emilie Bertil-Froidevaux Christophe Georger Nathalie Daniele Isabelle Richard David Israeli |
| author_facet | Nathalie Bourg Ai Vu Hong William Lostal Abbass Jaber Nicolas Guerchet Guillaume Tanniou Fanny Bordier Emilie Bertil-Froidevaux Christophe Georger Nathalie Daniele Isabelle Richard David Israeli |
| author_sort | Nathalie Bourg |
| collection | DOAJ |
| 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. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:45:16Z |
| publishDate | 2022-02-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b33d5a168eaa421083eccfe1b5d5b3d02023-11-23T20:18:26ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-02-01234201610.3390/ijms23042016Co-Administration of Simvastatin Does Not Potentiate the Benefit of Gene Therapy in the mdx Mouse Model for Duchenne Muscular DystrophyNathalie Bourg0Ai Vu Hong1William Lostal2Abbass Jaber3Nicolas Guerchet4Guillaume Tanniou5Fanny Bordier6Emilie Bertil-Froidevaux7Christophe Georger8Nathalie Daniele9Isabelle Richard10David Israeli11Généthon, 91000 Evry, FranceGénéthon, 91000 Evry, FranceGénéthon, 91000 Evry, FranceGénéthon, 91000 Evry, FranceGénéthon, 91000 Evry, FranceGénéthon, 91000 Evry, FranceGénéthon, 91000 Evry, FranceGénéthon, 91000 Evry, FranceGénéthon, 91000 Evry, FranceGénéthon, 91000 Evry, FranceGénéthon, 91000 Evry, FranceGénéthon, 91000 Evry, FranceDuchenne 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.https://www.mdpi.com/1422-0067/23/4/2016Duchenne muscular dystrophysimvastatingene therapyAAVmicrodystrophincombined therapy |
| spellingShingle | Nathalie Bourg Ai Vu Hong William Lostal Abbass Jaber Nicolas Guerchet Guillaume Tanniou Fanny Bordier Emilie Bertil-Froidevaux Christophe Georger Nathalie Daniele Isabelle Richard David Israeli Co-Administration of Simvastatin Does Not Potentiate the Benefit of Gene Therapy in the mdx Mouse Model for Duchenne Muscular Dystrophy International Journal of Molecular Sciences Duchenne muscular dystrophy simvastatin gene therapy AAV microdystrophin combined therapy |
| 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 | Duchenne muscular dystrophy simvastatin gene therapy AAV microdystrophin combined therapy |
| url | https://www.mdpi.com/1422-0067/23/4/2016 |
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