Testing a new drug to block ceramide and treat heart disease

Synthetic derivatives of Fenretinide, a novel approach to prevent lipotoxicity, insulin resistance and vascular endothelial dysfunction

Dr Nimesh Mody and his colleagues at the University of Aberdeen are designing a new drug that blocks the production of a fatty molecule called ceramide, which could be used to treat a range of diseases. Obesity, heart and circulatory disease and type 2 diabetes are common and closely linked medical conditions. One factor connecting these disorders is the over-production of several fatty molecules, one of which is ceramide. Dr Mody has recently discovered that a drug related to vitamin A, called fenretinide, can partially prevent or reduce obesity and type 2 diabetes in mice fed a high fat diet. Fenretinide appears to work by blocking ceramide production in fat tissue. In this project, Dr Mody will chemically change fenretinide to boost its beneficial effect of blocking ceramide levels but remove its other, potentially harmful, properties. He will then test this modified fenretinide in fat cells, tissues and in mice, with the hopes of improving blood glucose levels, and keeping blood vessels functioning properly. Dr Mody hopes this drug will safely prevent obesity linked to high-fat feeding and prevent the development of heart and circulatory disease and type 2 diabetes. This research could pave the way for new and better drugs to be developed that block the production of ceramide.