Potential new strategies for the treatment of kidney disease due to diabetes

Type-1 and type-2 diabetes are both characterised by poor blood glucose level control. This is associated with increased glucose production from the liver which ultimately leads to other complications including progressive loss of kidney function due to podocyte damage. Diabetic kidney disease, also known as diabetic nephropathy (DN) remains one of the leading causes of reduced lifespan in diabetes and is the leading cause of end-stage kidney disease, where dialysis and transplantation are the only options for survival. Consequently, there is a great unmet need for treatments to reduce DN development and progression. Active ingredients in the cannabis plant are known to have beneficial effects for treatment of conditions such as rheumatoid arthritis. They do this by acting on the “cannabinoid receptors” (CB1 and CB2), with CB1 receptors being expressed mainly in the brain and the CB2 receptors in the other tissues of the body, including the kidney. However, levels of CB1 receptors were recently reported to be increased and CB2 receptors decreased in DN. We aim to block the cannabinoid CB1 receptors and activate CB2 receptors with new cannabinoid drugs as a novel strategy for DN treatment. Our hypothesis, based on strong preliminary data, is that drugs that could block CB1 receptors and activate CB2 receptors in the kidney cells could present a novel therapeutic potential in treatment of DN. We will use commercial human and mouse kidney cells as our study model and treat these cells with cannabinoids, as well as rodent models of diabetes so that we can investigate the translational potential of these drugs.