Project 446662

Diabetes and osteoarthritis (OA) are two of the most common diseases affecting approximately 11 and 4 million Canadians, respectively. Diabetes can lead to multiple serious conditions including blindness, kidney failure, heart attack, and stroke. OA can cause chronic pain, make it challenging for individuals to walk, and to carry out normal activities of daily living such as getting dressed or bathing. Furthermore, both diabetes and OA are associated with depression and can significantly impact a person's quality of life. Despite how common and serious these conditions are, there is no cure or effective therapy for either. Therefore we must better understand their underlying causes to identify more effective treatment targets. Diabetes (specifically type 2 diabetes (T2D)) and OA often occur together and both are associated with a condition called sarcopenia. Sarcopenia refers to the loss of muscle mass and strength that occurs with aging. We therefore posit that sarcopenia serves as a common link between T2D and OA. Autophagy is a 'self-eating' process that 'cleans out' damaged components of cells. When autophagy is defective in muscle, damaged cell components can accumulate, and this can lead to sarcopenia. The purpose of this team project is to determine how problems with muscle autophagy contribute to T2D and OA. In order to do this, we will study mouse models in which genes regulating autophagy have been altered in muscle and examine for OA in these mice. We will also assess if we can treat or reverse T2D and OA using gene therapy to restore autophagy in muscle. Finally, we will take samples of muscle, blood, as well as knee x-rays from patients with these conditions and analyze them to identify common genetic links between T2D and OA to identify new drug targets. We have assembled a strong team of world leading scientists with expertise in all aspects of this proposed project to ensure feasibility of success towards more effective treatment and cure.