Duchenne muscular dystrophy (DMD) is a severe disorder characterised 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. In this study, the authors have revealed that tamoxifen, a drug used to treat oestrogen-dependent breast cancer, caused remarkable improvements of muscle force and of diaphragm and cardiac structure in the mdx5Cv mouse model of DMD. Oral tamoxifen treatment from 3 weeks of age for 15 months at a dose of 10 mg/kg/day stabilized myofibre 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, myofibre count, and myofibre 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 oestrogen receptors ERα and ERβ were several times more abundant in dystrophic than in normal muscles, and tamoxifen normalised the relative abundance of ERβ isoforms. These findings suggest that tamoxifen might be a useful therapy for DMD.
