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.
Résumé
Plus d’un siècle après que le médecin allemand Paul Ehrlich a avancé l’idée d’un «
projectile magique » capable de trouver et de neutraliser les agents pathogènes présents
dans l’organisme, les premiers anticorps monoclonaux visant à réduire le taux de cholestérol
des lipoprotéines de basse densité (C-LDL) ont fait leur apparition dans l’usage clinique.
Cette nouvelle classe d’agents hypolipidémiants cible la proprotéine convertase subtilisine/kexine
de type 9 (PCSK9), une enzyme qui se fixe aux récepteurs des LDL (LDLR) hépatiques
et induit la dégradation intracellulaire, réduisant ainsi l’endocytose provoquée par
les LDLR et l’élimination du C-LDL de la circulation. Ces nouveaux médicaments sont
les premiers anticorps monoclonaux destinés au traitement cardiovasculaire à long
terme. Dans cet article, nous passons en revue l’historique de la mise au point des
anticorps monoclonaux et du choix de la PCSK9 comme cible, ainsi que les données actuelles
relatives à l’innocuité et à l’efficacité et le statut réglementaire de ces nouveaux
agents thérapeutiques. Nous adressons aussi quelques conseils aux cliniciens sur le
rôle que ces nouveaux médicaments pourraient jouer dans la pratique clinique.
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Article info
Publication history
Published online: May 03, 2016
Accepted:
April 26,
2016
Received:
March 31,
2016
Footnotes
See page 1559 for disclosure information.
Identification
Copyright
© 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
