As there are no effective treatments for muscular dystrophy (MD), identifying systemically acting small-molecule therapeutics is desirable. Tyrosine phosphorylation of β-dystroglycan, which occurs via tyrosine kinase in dystrophin-deficient muscles, has been reported to induce muscle damage, and several tyrosine kinase inhibitors have been researched as potential therapeutic agents for MD. Nilotinib, a second-generation tyrosine kinase inhibitor, was potentially effective in MD by reducing muscle fibrosis. However, there was a problem that its direct effect on satellite cells inhibited muscle differentiation. Dasatinib, a third-generation tyrosine kinase inhibitor, is also expected to be effective in MD, but its effect on muscle regeneration is unknown.
Here, we investigated the effects of dasatinib on muscle, with a focus on muscle regeneration. We administered dasatinib to mice whose tibialis anterior muscle was damaged by cardiotoxin. In the dasatinib-treated mice, abnormal myofibers were observed, and muscle regeneration may be impaired. The effect on muscle differentiation was examined using the myoblast cell line C2C12. There was abnormal cell fusion, and this abnormality differed from that previously described for nilotinib. Further research is currently underway into mechanisms causing the abnormal muscle regeneration.