Pharmacological inhibition of USP19 deubiquitinating enzyme as a novel therapy for muscle wasting

Muscle wasting is a common complication of many diseases such as cancer, chronic heart and lung disease and results in weakness, impaired quality of life and shortened survival. There are no drugs for the treatment of muscle wasting. We have identified a gene, USP19, in the ubiquitin pathway which is the major pathway of protein breakdown in cells. USP19 is activated in rodents in skeletal muscle wasting from many catabolic conditions. Mice lacking USP19 lose less muscle mass and strength in several conditions of muscle wasting. Therefore, inhibiting USP19 is an attractive new approach to the treatment of muscle wasting. We propose here to test whether a new inhibitor of USP19 discovered by Almac Discovery prevents muscle wasting in mice. We will also perform studies to understand how this inhibitor works. These studies may lead to the development of this inhibitor into a drug for the treatment of muscle wasting.

Intern: 
Erin Coyne
Faculty Supervisor: 
Simon Wing
Province: 
Quebec
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