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Updated: Mar 16, 2026

A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9
Published on: August 28, 2018
Monoclonal Antibodies for the Treatment of Hypercholesterolemia: Targeting PCSK9
Manal Alkindi1, Katherine A Siminovitch2, Milan Gupta3
1Cardiovascular Research Laboratories, Research Institute of the McGill University Health Centre, Montréal, Québec, Canada.
Abstract:
More than a century after German physician Paul Ehrlich put forth the idea of a "magic bullet" that could seek out and neutralize disease-causing agents in the body, the first monoclonal antibodies (mAbs) to lower low-density lipoprotein cholesterol (LDL-C) have been introduced into clinical use. This novel class of lipid-lowering agents targets proprotein convertase subtilisin/kexin type 9 (PCSK9), an enzyme that chaperones hepatic LDL receptors (LDLRs) toward intracellular degradation, reducing LDLR-mediated endocytosis and the clearance of LDL-C from the circulation. These new drugs represent the first mAb therapy intended for long-term cardiovascular use. We review the development of mAbs, the selection of PCSK9 as a target, and the current safety and efficacy data and regulatory status of these new therapeutic agents. We also provide guidance to clinicians regarding the potential role for these new agents in clinical practice.
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