A new study suggests that a drug already approved by the US Food and Drug Administration (FDA) for the treatment of certain types of cancer could also have a benefit for people with Duchenne muscular dystrophy.
With funds provided by Muscular Dystrophy UK and other organisations, Professor Steve Winder and his team showed that dasatinib improves muscle function in a zebrafish model of Duchenne muscular dystrophy.
The results are very encouraging and present a possible new avenue for the treatment of Duchenne muscular dystrophy that is independent of the dystrophin gene itself. The drug is already approved for use in humans so could soon be tested in clinical trials for Duchenne muscular dystrophy.
However it should be noted that the experiments were only performed on zebrafish; they will need to be validated in mouse models before the drug can be taken into human clinical trials.
We work closely with Prof Winder, who has told us that his group are already testing the effects of dasatinib in mice. We look forward to the results from these experiments and will keep our supporters updated on any advances.
Dystrophin is a vital protein found under the muscle cell membrane and anchors molecules from inside the cell to proteins on the cell membrane. In the absence of dystrophin (as in the case of Duchene muscular dystrophy) one of the proteins in the muscle cell membrane called beta-dystroglycan, is ‘marked’ and destroyed by the cell. This disrupts the integrity of the muscle cell membrane and the muscle cell dies.
Prof Winder and co-workers tested a number of small molecules that could inhibit the degradation process of the beta-dystroglycan protein. One such molecule is called dasatinib and is already being used as a drug to treat certain types of cancer.
Using a zebrafish model of Duchenne muscular dystrophy, Prof Winder and his team have shown that dasatinib prevents the cell from making the ‘mark’ on beta-dystroglycan that leads to its destruction. This allows beta-dystroglycan to be preserved in the muscle cell membrane even in the absence of dystrophin.
Zebrafish is a great animal model to test new drugs and compounds as these can be directly added to the fish water. It is also easier and cheaper to keep compared to higher organisms such as mice.
The fish that is used to model Duchenne muscular dystrophy, the sapje fish, has a mutation in the dystrophin gene just like people affected by the condition. This means that no dystrophin protein is made. As a result of this, the sapje fish are considerably poorer at swimming.
The researchers showed that dasatinib significantly increased the total distance swum in ten minutes by the sapje fish. This test could be compared to the six-minute walk test in boys with Duchenne muscular dystrophy.
A universal small molecule or drug that is easily administered and that acts on all muscles in the body would be an enormous advance for the treatment of Duchenne muscular dystrophy.
This piece of research shows that dasatinib, a drug already used to treat certain types of cancer can also be beneficial for Duchenne muscular dystrophy.
The research showed only a partial rescue of the dystrophic phenotype in the fish. However if this was to be translated to the human condition even a small reduction in the symptoms can have big effects on the quality of life of people with Duchenne muscular dystrophy.
It is important to note that these experiments were performed on zebrafish and even though it is a great animal model the results would need to be tested in a higher organism such as mouse before the drug can be tested in human clinical trials.
The fact that dasatinib is already approved by the FDA to be used in people is promising and could mean that trials testing its effect in people with Duchenne muscular dystrophy could start sooner.
Duchenne muscular dystrophy is a muscle-wasting condition caused by the lack of a vital protein called dystrophin. There are currently no effective treatments for this life-limiting condition.
Read about the project we funded in Prof Winder’s laboratory
Read about other research projects on Duchenne muscular dystrophy
Read our other research news about Duchenne muscular dystrophy
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