The teams have identified the molecular target for the utrophin modulator drug, ezutromid. Utrophin is a protein related to dystrophin, which is the protein that is absent in the muscle-wasting condition Duchenne muscular dystrophy (DMD). It has the potential to act as a substitute for dystrophin. The drug was originally designed to treat DMD by increasing the amount of utrophin in muscle cells.
Summit Therapeutics began a clinical trial to test whether ezutromid would be a beneficial treatment for boys with DMD. The clinical trial showed promising results after 24 weeks of treatment. However, the drug wasn’t effective over a longer period and in 2018, Summit discontinued its development. This was, understandably, very disappointing for the many families who had been involved in the clinical trial.
Having a better understanding of how ezutromid works could help to uncover new opportunities for alternative drugs that might act in a similar yet more effective way. The researchers demonstrated that the drug binds to a protein, called the aryl hydrocarbon receptor, leading to more utrophin production. This could provide a new lead for the development of utrophin replacement therapy.
Dr Kate Adcock, Director of Research and Innovation at Muscular Dystrophy UK, said:
These results provide the next step in the development of a utrophin replacement therapy to treat Duchenne muscular dystrophy. They demonstrate the importance of laboratory research to inform the development of drugs. We are excited by the results and future prospects
Professor Angela Russell, University of Oxford, said:
Our study has deepened our understanding of mechanism of action of ezutromid. By discovering the link between the aryl hydrocarbon receptor and the drug, we have demonstrated the potential to improve the efficacy of utrophin up-regulating drugs in the future
To find out more, read the scientific paper.