Anti-sense Therapy Against ApoC-III as a Treatment for High Cholesterol

This technology includes a new class of synthetic peptides that activate Lipoprotein Lipase (LPL), a key plasma enzyme that lowers triglycerides, by displacing apoC-111, a potent inhibitor of LPL. ApoC-11 is a known activator of LPL, whereas ApoC-111 inhibits LPL and raises triglycerides either directly by blocking lipolysis and or by preventing hepatic uptake of lipoproteins. Both apoC-II and apoC-III have to bind to the surface of a lipoprotein particle to mediate their effects. We discovered that we can displace apoC-III from lipoproteins and improve lipolysis by adding short synthetic peptide mimetics of apoC-II. These peptides are described in another EIR. Anti-sense therapy against apoC-111 has been shown in late-stage clinical trials to be useful for a wide variety of causes of hypertriglyceridemia, including LPL deficiency, thus our new peptides that antagonize apoC-III can be an alternative approach.