Patients with hypertriglyceridemia have an increased risk of morbidity and mortality due to coronary heart disease (CHD). Among type 2 diabetics the risk is two to four times greater than non-diabetic patients. These individuals typically have elevated triglycerides, reduced HDL cholesterol, and near normal LDL cholesterol with increased numbers of small, dense LDL particles. A similar pattern is often seen in patients with existing CHD. Currently available agents do not specifically target reductions in serum triglycerides, but more commonly target reductions in LDL cholesterol. IDD has identified a template molecule with modest in vivo efficacy that specifically lowers triglycerides. We have outlined a comprehensive program involving optimization of innovative chiral synthetic methods and evaluation of novel analogues to determine the feasibility of identifying unique compounds with improved efficacy. The identification and development of a specific treatment for hypertriglyceridemia will lead to substantial reductions in coronary heart disease and atherosclerotic complications. PROPOSED COMMERCIAL APPLICATIONS: Estimated costs for treatment and losses attributable to coronary heart disease (CHD) in the United States are $100 billion annually. Nearly 500,000 individuals die annually from CHD. The role of elevated lipids in the development of CHD is well recognized. Despite the fact that approximately 45% of persons at risk with elevated lipids have elevated triglycerides with little or no increase in total cholesterol, currently available drugs fail to target this population. The development of a specific therapeutic agent which targets this patient population will fill an unmet medical need of significant commercial opportunity.
