Targeting PCSK9 for hypercholesterolemia

Giuseppe Danilo Norata, Gianpaolo Tibolla, Alberico Luigi Catapano

Research output: Contribution to journalArticle

Abstract

Dyslipidemias are a predominant risk factor for cardiovascular disease. Biological and genetic research has led to the identification of several genes and proteins that may be pharmacologically targeted to improve lipoprotein profiles and possibly cardiovascular outcomes in patients with dyslipidemia. The observation that proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates the levels of circulating low-density lipoprotein C (LDL-C) by enhancing the degradation of the hepatic low-density lipoprotein receptor (LDLR) prompted the search for drugs that inhibit PCSK9 activity. Several approaches to inhibiting PCSK9 activity have been proposed; these involve inhibitory antibodies, small molecules, and gene silencing. To date, the most promising and advanced approach relates to monoclonal antibodies, which can decrease LDL cholesterol by 65-70%, even as an add-on therapy to a maximal dose of a statin. Phase III studies and large, event-driven clinical trials are ongoing and will fully address the viability and role of these drugs in clinical practice.

Original languageEnglish
Pages (from-to)273-293
Number of pages21
JournalAnnual Review of Pharmacology and Toxicology
Volume54
DOIs
Publication statusPublished - 2014

Fingerprint

Proprotein Convertases
Subtilisin
Hypercholesterolemia
Dyslipidemias
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Genetic Research
LDL Receptors
Gene Silencing
LDL Lipoproteins
Pharmaceutical Preparations
LDL Cholesterol
Lipoproteins
Cardiovascular Diseases
Genes
Monoclonal Antibodies
Clinical Trials
Degradation
Molecules
Antibodies
Liver

Keywords

  • LDL cholesterol
  • LDL receptor
  • LDLR
  • MAbs
  • Monoclonal antibodies

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Targeting PCSK9 for hypercholesterolemia. / Norata, Giuseppe Danilo; Tibolla, Gianpaolo; Catapano, Alberico Luigi.

In: Annual Review of Pharmacology and Toxicology, Vol. 54, 2014, p. 273-293.

Research output: Contribution to journalArticle

Norata, Giuseppe Danilo ; Tibolla, Gianpaolo ; Catapano, Alberico Luigi. / Targeting PCSK9 for hypercholesterolemia. In: Annual Review of Pharmacology and Toxicology. 2014 ; Vol. 54. pp. 273-293.
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