Leukemia drug dasatinib shows promise for treating duchenne muscular dystrophy

Professor Winder's group at the University of Sheffield investigating the cancer drug, dasatinib, a potent and specific Src tyrosine kinase inhibitor has shown that it decreases the levels of β-dystroglycan phosphorylation on tyrosine and to increase the relative levels of non-phosphorylated β-dystroglycan in dystrophic sapje zebrafish. Tyrosine phosphorylation and degradation of β-dystroglycan is a key event in the aetiology of Duchenne muscular dystrophy.

Dasatinib treatment resulted in the improved physical appearance of the sapje zebrafish musculature and increased swimming ability as measured by both duration and distance of swimming of dasatinib-treated fish compared with control animals. These findings show great promise for pharmacological agents that prevent the phosphorylation of β-dystroglycan on tyrosine and subsequent steps in the degradation pathway as therapeutic targets for the treatment of Duchenne muscular dystrophy.The results are published in the journal Human Molecular Genetics.

Since dasatinib is already cleared for clinical use in Leukemia, researchers are hopeful that progress can be made more quickly towards trialling the drug in humans as a treatment for DMD. It could be that by combining the drug with other treatments currently under development, their effectiveness could be improved even further. Experiments have already begun in mice models, with promising results.

Citation: Lipscomb L, Piggott RW, Emmerson T, Winder SJ (2015) Dasatinib as a treatment for Duchenne muscular dystrophy.Hum Mol Genet ():. DOI: 10.1093/hmg/ddv469 PMID: 26604135.

Cover image: Muscle birefringence images from wild type, mild, moderate and severely affected sapje fish.