The anticancer drug tamoxifen counteracts the pathology in a mouse model of duchenne muscular dystrophy.

Détails

ID Serval
serval:BIB_FDDDD54C235C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
The anticancer drug tamoxifen counteracts the pathology in a mouse model of duchenne muscular dystrophy.
Périodique
American Journal of Pathology
Auteur(s)
Dorchies O.M., Reutenauer-Patte J., Dahmane E., Ismail H.M., Petermann O., Patthey- Vuadens O., Comyn S.A., Gayi E., Piacenza T., Handa R.J., Décosterd L.A., Ruegg U.T.
ISSN
1525-2191 (Electronic)
ISSN-L
0002-9440
Statut éditorial
Publié
Date de publication
2013
Volume
182
Numéro
2
Pages
485-504
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
Duchenne muscular dystrophy (DMD) is a severe disorder characterized by progressive muscle wasting,respiratory and cardiac impairments, and premature death. No treatment exists so far, and the identification of active substances to fight DMD is urgently needed. We found that tamoxifen, a drug used to treat estrogen-dependent breast cancer, caused remarkable improvements of muscle force and of diaphragm and cardiac structure in the mdx(5Cv) mouse model of DMD. Oral tamoxifen treatment from 3 weeks of age for 15 months at a dose of 10 mg/kg/day stabilized myofiber membranes, normalized whole body force, and increased force production and resistance to repeated contractions of the triceps muscle above normal values. Tamoxifen improved the structure of leg muscles and diminished cardiac fibrosis by~ 50%. Tamoxifen also reduced fibrosis in the diaphragm, while increasing its thickness,myofiber count, and myofiber diameter, thereby augmenting by 72% the amount of contractile tissue available for respiratory function. Tamoxifen conferred a markedly slower phenotype to the muscles.Tamoxifen and its metabolites were present in nanomolar concentrations in plasma and muscles,suggesting signaling through high-affinity targets. Interestingly, the estrogen receptors ERa and ERb were several times more abundant in dystrophic than in normal muscles, and tamoxifen normalized the relative abundance of ERb isoforms. Our findings suggest that tamoxifen might be a useful therapy for DMD.
Pubmed
Web of science
Open Access
Oui
Création de la notice
07/03/2013 18:21
Dernière modification de la notice
20/08/2019 16:28
Données d'usage