Universität zu Köln

Gouni-Berthold, Ioanna and Berthold, Heiner K. (2014). PCSK9 Antibodies for the Treatment of Hypercholesterolemia. Nutrients, 6 (12). S. 5517 - 5534. BASEL: MDPI AG. ISSN 2072-6643

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Abstract

The serine protease proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low-density lipoprotein (LDL) receptor (LDLR) and directs it to lysosomes for intracellular degradation. This results in decreased numbers of LDLR available on the hepatic cell surface to bind LDL particles and remove them from the circulation and therefore to a subsequent increase in circulating LDL-cholesterol (LDL-C) plasma levels. Since 2003, when the role of PCSK9 in LDL-C metabolism was discovered, there have been major efforts to develop efficient and safe methods to inhibit it. Amongst those, monoclonal antibodies against PCSK9 are the furthest in development, with multiple phase 3 trials already published and with cardiovascular endpoint trials currently underway. Two fully human monoclonal antibodies, evolocumab (AMG 145) and alirocumab (REGN727/SAR236553), have been extensively studied in a wide range of subjects, such as those with statin intolerance, as an add-on to statin therapy, as a monotherapy and in patients with familial hypercholesterolemia. PCSK9 antibodies result in a consistent and robust decrease in LDL-C plasma levels ranging from 40% to 70%, either on top of statins or as a monotherapy. If the safety data from the on-going phase 3 trials remain as reassuring as the data available till now, PCSK9 antibodies will offer a novel, powerful therapeutic option to decrease LDL-C plasma levels and, hopefully, cardiovascular risk.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Gouni-Berthold, Ioanna UNSPECIFIED UNSPECIFIED UNSPECIFIED Berthold, Heiner K. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-421417
DOI:	10.3390/nu6125517
Journal or Publication Title:	Nutrients
Volume:	6
Number:	12
Page Range:	S. 5517 - 5534
Date:	2014
Publisher:	MDPI AG
Place of Publication:	BASEL
ISSN:	2072-6643
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DENSITY-LIPOPROTEIN CHOLESTEROL; SUBTILISIN/KEXIN TYPE 9; EVOLOCUMAB AMG 145; HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA; MONOCLONAL-ANTIBODY; DOUBLE-BLIND; RANDOMIZED-TRIAL; LDL-C; HEALTHY-VOLUNTEERS; SERINE-PROTEASE Multiple languages Nutrition & Dietetics Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/42141