IPRD funded research by Choogon Lee
Pediatric hypercholesterolemia: High cholesterol level in blood is associated with atherosclerotic plaques and is a major risk factor for cardiovascular disease. Dietary control alone cannot control high cholesterol in some patients who have abnormal endogenous cholesterol synthesis due to mutations in genes encoding rate-limiting enzymes in the endogenous pathway. One example is rare familial hypercholesterolemia in which patients have mutations in the LDLR (LDL receptor), LDLRAP1 (LDL receptor associated protein 1), PCSK9 (a chaperone protein for LDL receptor degradation) and APOB100 (the limiting apoprotein for LDL formation), genes. Many patients are statin intolerant due to liver and muscle toxicity. In some cases, even high-intensity statin therapy is simply ineffective. Recent research has identified HMG-Co-A reductase, LDLR and PCSK9 as potential drug targets for hypercholesterolemia. This research project will identify small molecule drugs for currently known targets and develop new drug targets for familial hypercholesterolemia.
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