Cargando…
Simvastatin Treatment Does Not Ameliorate Muscle Pathophysiology in a Mouse Model for Duchenne Muscular Dystrophy
Duchenne muscular dystrophy is an X-linked, recessive muscular dystrophy in which the absence of the dystrophin protein leads to fibrosis, inflammation and oxidative stress, resulting in loss of muscle tissue. Drug repurposing, i.e. using drugs already approved for other disorders, is attractive as...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
IOS Press
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8543260/ https://www.ncbi.nlm.nih.gov/pubmed/33044191 http://dx.doi.org/10.3233/JND-200524 |
_version_ | 1784589605395234816 |
---|---|
author | Verhaart, Ingrid E.C. Cappellari, Ornella Tanganyika-de Winter, Christa L. Plomp, Jaap J. Nnorom, Sofia Wells, Kim E. Hildyard, John C.W. Bull, David Aartsma-Rus, Annemieke Wells, Dominic J. |
author_facet | Verhaart, Ingrid E.C. Cappellari, Ornella Tanganyika-de Winter, Christa L. Plomp, Jaap J. Nnorom, Sofia Wells, Kim E. Hildyard, John C.W. Bull, David Aartsma-Rus, Annemieke Wells, Dominic J. |
author_sort | Verhaart, Ingrid E.C. |
collection | PubMed |
description | Duchenne muscular dystrophy is an X-linked, recessive muscular dystrophy in which the absence of the dystrophin protein leads to fibrosis, inflammation and oxidative stress, resulting in loss of muscle tissue. Drug repurposing, i.e. using drugs already approved for other disorders, is attractive as it decreases development time. Recent studies suggested that simvastatin, a cholesterol lowering drug used for cardiovascular diseases, has beneficial effects on several parameters in mdx mice. To validate properly the effectiveness of simvastatin, two independent labs tested the effects of 12-week simvastatin treatment in either young (starting at 4 weeks of age) or adult (starting at 12 weeks of age) mdx mice. In neither study were benefits of simvastatin treatment observed on muscle function, histology or expression of genes involved in fibrosis, regeneration, oxidative stress and autophagy. Unexpectedly, although the treatment protocol was similar, simvastatin plasma levels were found to be much lower than observed in a previous study. In conclusion, in two laboratories, simvastatin did not ameliorate disease pathology in mdx mice, which could either be due to the ineffectiveness of simvastatin itself or due to the low simvastatin plasma levels following oral administration via the food. |
format | Online Article Text |
id | pubmed-8543260 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | IOS Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-85432602021-11-10 Simvastatin Treatment Does Not Ameliorate Muscle Pathophysiology in a Mouse Model for Duchenne Muscular Dystrophy Verhaart, Ingrid E.C. Cappellari, Ornella Tanganyika-de Winter, Christa L. Plomp, Jaap J. Nnorom, Sofia Wells, Kim E. Hildyard, John C.W. Bull, David Aartsma-Rus, Annemieke Wells, Dominic J. J Neuromuscul Dis Research Report Duchenne muscular dystrophy is an X-linked, recessive muscular dystrophy in which the absence of the dystrophin protein leads to fibrosis, inflammation and oxidative stress, resulting in loss of muscle tissue. Drug repurposing, i.e. using drugs already approved for other disorders, is attractive as it decreases development time. Recent studies suggested that simvastatin, a cholesterol lowering drug used for cardiovascular diseases, has beneficial effects on several parameters in mdx mice. To validate properly the effectiveness of simvastatin, two independent labs tested the effects of 12-week simvastatin treatment in either young (starting at 4 weeks of age) or adult (starting at 12 weeks of age) mdx mice. In neither study were benefits of simvastatin treatment observed on muscle function, histology or expression of genes involved in fibrosis, regeneration, oxidative stress and autophagy. Unexpectedly, although the treatment protocol was similar, simvastatin plasma levels were found to be much lower than observed in a previous study. In conclusion, in two laboratories, simvastatin did not ameliorate disease pathology in mdx mice, which could either be due to the ineffectiveness of simvastatin itself or due to the low simvastatin plasma levels following oral administration via the food. IOS Press 2021-09-14 /pmc/articles/PMC8543260/ /pubmed/33044191 http://dx.doi.org/10.3233/JND-200524 Text en © 2021 – The authors. Published by IOS Press https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Report Verhaart, Ingrid E.C. Cappellari, Ornella Tanganyika-de Winter, Christa L. Plomp, Jaap J. Nnorom, Sofia Wells, Kim E. Hildyard, John C.W. Bull, David Aartsma-Rus, Annemieke Wells, Dominic J. Simvastatin Treatment Does Not Ameliorate Muscle Pathophysiology in a Mouse Model for Duchenne Muscular Dystrophy |
title | Simvastatin Treatment Does Not Ameliorate Muscle Pathophysiology in a Mouse Model for Duchenne Muscular Dystrophy |
title_full | Simvastatin Treatment Does Not Ameliorate Muscle Pathophysiology in a Mouse Model for Duchenne Muscular Dystrophy |
title_fullStr | Simvastatin Treatment Does Not Ameliorate Muscle Pathophysiology in a Mouse Model for Duchenne Muscular Dystrophy |
title_full_unstemmed | Simvastatin Treatment Does Not Ameliorate Muscle Pathophysiology in a Mouse Model for Duchenne Muscular Dystrophy |
title_short | Simvastatin Treatment Does Not Ameliorate Muscle Pathophysiology in a Mouse Model for Duchenne Muscular Dystrophy |
title_sort | simvastatin treatment does not ameliorate muscle pathophysiology in a mouse model for duchenne muscular dystrophy |
topic | Research Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8543260/ https://www.ncbi.nlm.nih.gov/pubmed/33044191 http://dx.doi.org/10.3233/JND-200524 |
work_keys_str_mv | AT verhaartingridec simvastatintreatmentdoesnotamelioratemusclepathophysiologyinamousemodelforduchennemusculardystrophy AT cappellariornella simvastatintreatmentdoesnotamelioratemusclepathophysiologyinamousemodelforduchennemusculardystrophy AT tanganyikadewinterchristal simvastatintreatmentdoesnotamelioratemusclepathophysiologyinamousemodelforduchennemusculardystrophy AT plompjaapj simvastatintreatmentdoesnotamelioratemusclepathophysiologyinamousemodelforduchennemusculardystrophy AT nnoromsofia simvastatintreatmentdoesnotamelioratemusclepathophysiologyinamousemodelforduchennemusculardystrophy AT wellskime simvastatintreatmentdoesnotamelioratemusclepathophysiologyinamousemodelforduchennemusculardystrophy AT hildyardjohncw simvastatintreatmentdoesnotamelioratemusclepathophysiologyinamousemodelforduchennemusculardystrophy AT bulldavid simvastatintreatmentdoesnotamelioratemusclepathophysiologyinamousemodelforduchennemusculardystrophy AT aartsmarusannemieke simvastatintreatmentdoesnotamelioratemusclepathophysiologyinamousemodelforduchennemusculardystrophy AT wellsdominicj simvastatintreatmentdoesnotamelioratemusclepathophysiologyinamousemodelforduchennemusculardystrophy |