ANGPTL3 as therapeutic target

Purpose of review: Elevated LDL-C and triglycerides are important risk factors for the development of atherosclerotic cardiovascular disease. Although effective therapies for lipid lowering exist, many people do not reach their treatment targets. In the last two decades, ANGPTL3 has emerged as a novel therapeutic target for lowering plasma LDL-C and triglycerides. Here, an overview of the recent literature on ANGPTL3 is provided, focusing on the therapeutic benefits of inactivation of ANGPTL3 via monoclonal antibodies, antisense oligonucleotides, and other more nascent approaches. In addition, the potential mechanisms by which ANGPTL3 inactivation lowers plasma LDL-C are discussed.

Recent findings: ANGPTL3 is a factor secreted by the liver that inhibits lipoprotein lipase and other lipases via the formation of a complex with the related protein ANGPTL8. Large-scale genetic studies in humans have shown that carriers of loss-of-function variants in ANGPTL3 have lower plasma LDL-C and triglyceride levels, and are at reduced risk of atherosclerotic cardiovascular disease. Clinical studies in patients with different forms of dyslipidemia have demonstrated that inactivation of ANGPTL3 using monoclonal antibodies or antisense oligonucleotides markedly lowers plasma LDL-C and triglyceride levels.

Summary: Anti-ANGPTL3 therapies hold considerable promise for reducing plasma LDL-C and triglycerides in selected patient groups.