Living the PCSK9 Adventure: from the Identification of a New Gene in Familial Hypercholesterolemia Towards a Potential New Class of Anticholesterol Drugs

Marianne Abifadel, Sandy Elbitar, Petra EL Khoury, Youmna Ghaleb, Melody El Chemaly, Marie-Line Moussalli, Jean-Pierre Rabes, Mathilde Varret, Catherine Boileau

Research output: Contribution to journalReview article

64 Citations (Scopus)


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.
Original languageEnglish
Article number16:439
Number of pages23
JournalCurrent Atherosclerosis Reports
Issue number439
Early online date23 Jul 2014
Publication statusPublished - Sep 2014



  • Hypercholesterolemia
  • LDLR
  • PCSK9
  • Gain of function mutations
  • Loss of function
  • Evolocumab
  • Alirocumab

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