title: Monoclonal Antibodies for the Treatment of Hypercholesterolemia: Targeting PCSK9.
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.
authors: Cardiovascular Research Laboratories, Research Institute of the McGill University Health Centre, Montréal, Québec, Canada.
authors: Manal
authors: M
authors: Alkindi
authors: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
authors: Katherine A
authors: KA
authors: Siminovitch
authors: Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors: Milan
authors: M
authors: Gupta
authors: Cardiovascular Research Laboratories, Research Institute of the McGill University Health Centre, Montréal, Québec, Canada. Electronic address: jacques.genest@mcgill.ca.
authors: Jacques
authors: J
authors: Genest
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000924:Anticholesteremic Agents / Q000494:pharmacology; D004335:Drug and Narcotic Control; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy / Q000378:metabolism; D058990:Molecular Targeted Therapy / Q000379:methods; D000091362:PCSK9 Inhibitors; D017410:Practice Guidelines as Topic; D000071449:Proprotein Convertase 9 / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000924:Anticholesteremic Agents; D000091362:PCSK9 Inhibitors; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9