دورية أكاديمية
Co-Administration of Simvastatin Does Not Potentiate the Benefit of Gene Therapy in the mdx Mouse Model for Duchenne Muscular Dystrophy
| العنوان: | Co-Administration of Simvastatin Does Not Potentiate the Benefit of Gene Therapy in the mdx Mouse Model for Duchenne Muscular Dystrophy |
|---|---|
| المؤلفون: | 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 |
| المصدر: | International Journal of Molecular Sciences, Vol 23, Iss 4, p 2016 (2022) |
| بيانات النشر: | MDPI AG, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Biology (General) LCC:Chemistry |
| مصطلحات موضوعية: | Duchenne muscular dystrophy, simvastatin, gene therapy, AAV, microdystrophin, combined therapy, Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1422-0067 1661-6596 |
| Relation: | https://www.mdpi.com/1422-0067/23/4/2016; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067 |
| DOI: | 10.3390/ijms23042016 |
| URL الوصول: | https://doaj.org/article/b33d5a168eaa421083eccfe1b5d5b3d0 |
| رقم الأكسشن: | edsdoj.b33d5a168eaa421083eccfe1b5d5b3d0 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14220067 16616596 |
|---|---|
| DOI: | 10.3390/ijms23042016 |