title: Living the PCSK9 adventure: from the identification of a new gene in familial hypercholesterolemia towards a potential new class of anticholesterol drugs.
abstract: A decade after our discovery of the involvement of proprotein convertase subtilisin/kexin type 9 (PCSK9) in cholesterol metabolism through the identification of the first mutations leading to hypercholesterolemia, PCSK9 has become one of the most promising targets in cholesterol and cardiovascular diseases. This challenging work in the genetics of hypercholesterolemia paved the way for a plethora of studies around the world allowing the characterization of PCSK9, its expression, its impact on reducing the abundance of LDL receptor, and the identification of loss-of-function mutations in hypocholesterolemia. We highlight the different steps of this adventure and review the published clinical trials especially those with the anti-PCSK9 antibodies evolocumab (AMG 145) and alirocumab (SAR236553/REGN727), which are in phase III trials. The promising results in lowering LDL cholesterol levels raise hope that the PCSK9 adventure will lead, after the large and long-term ongoing phase III studies evaluating efficacy and safety, to a new anticholesterol pharmacological class.
authors: Laboratoire de Biochimie et Thérapies Moléculaires, Faculté de Pharmacie et Pôle Technologie - Santé, Université Saint-Joseph, Beirut, Lebanon, marianne.abi-fadel@inserm.fr.
authors: Marianne
authors: M
authors: Abifadel
authors: Sandy
authors: S
authors: Elbitar
authors: Petra
authors: P
authors: El Khoury
authors: Youmna
authors: Y
authors: Ghaleb
authors: Mélody
authors: M
authors: Chémaly
authors: Marie-Line
authors: ML
authors: Moussalli
authors: Jean-Pierre
authors: JP
authors: Rabès
authors: Mathilde
authors: M
authors: Varret
authors: Catherine
authors: C
authors: Boileau
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D020022:Genetic Predisposition to Disease; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000235:genetics*; D020127:Recovery of Function / Q000235:genetics*; D012697:Serine Endopeptidases / Q000235:genetics*
chemical_list: D000924:Anticholesteremic Agents; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases