Alagebrium Shows Potential in Diabetes-Related GI Complications

Synvista Therapeutics has published positive preclinical data demonstrating the ability of its compound, alagebrium, to reduce serum levels of advanced glycated end-products and restore neuronal nitric oxide synthase activity in rats with diabetes.

Loss of gastrointestinal neuronal nitric oxide synthase (nNOS) activity is one of the major putative mechanisms for the development of diabetic complications involving the gut, including gastroparesis and intestinal dysfunction and has been the subject of both intense investigation and thorough review.

Diabetic gastroparesis is a motility disorder in which the stomach takes too long to empty its contents. It is a disease of significant unmet medical need, as no pharmaceutical products are approved for the treatment of this condition.

Patients with diabetes commonly experience gastric and intestinal dysfunction, however, the mechanism of how this happens is not well understood. The term diabetic enteropathy is often used to explain the disturbance in bowel function such as chronic diarrhea which occurs in 15% or more diabetics. A role for decreased nNOS expression has been suggested as a possible cause for the diarrhea; however, how diabetes causes such changes in nNOS expression levels is unknown.