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

  • Marianne AbifadelEmail author
  • Sandy Elbitar
  • Petra El Khoury
  • Youmna Ghaleb
  • Mélody Chémaly
  • Marie-Line Moussalli
  • Jean-Pierre Rabès
  • Mathilde Varret
  • Catherine Boileau
Rare Diseases and Lipid Metabolism (JAG López, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Rare Diseases and Lipid Metabolism


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.


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



This work was supported by a grant from Fondation-Leducq (FLQ # 13 CVD 03) through the Transatlantic Networks of Excellence in Cardiovascular Research program (“The function and regulation of PCSK9: a novel modulator of LDLR activity”); Institut National de la Santé et de la Recherche Médicale (INSERM); Conseil de la Recherche de l’Université Saint-Joseph (Beirut, Lebanon), and Conseil National de la Recherche Scientifique Libanais.

Compliance with Ethics Guidelines

Conflict of Interest

Marianne Abifadel is member of the advisory board of Amgen and is involved in anti-PCSK9 studies and trials with Amgen and with Regeneron and Sanofi. Jean-Pierre Rabès and Catherine Boileau are involoved in anti-PCSK9 studies with Regeneron and Sanofi.

Sandy Elbitar, Petra El Khoury, Youmna Ghaleb, Mélody Chémaly, Marie-Line Moussalli, and Mathilde Varret declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Marianne Abifadel
    • 1
    • 2
    Email author
  • Sandy Elbitar
    • 1
  • Petra El Khoury
    • 1
    • 3
  • Youmna Ghaleb
    • 1
    • 2
  • Mélody Chémaly
    • 1
  • Marie-Line Moussalli
    • 1
  • Jean-Pierre Rabès
    • 2
    • 4
    • 5
  • Mathilde Varret
    • 2
    • 6
  • Catherine Boileau
    • 2
    • 6
    • 7
  1. 1.Laboratoire de Biochimie et Thérapies Moléculaires, Faculté de Pharmacie et Pôle Technologie - SantéUniversité Saint-JosephBeirutLebanon
  2. 2.INSERM U1148Hôpital Xavier-BichatParis Cedex 18France
  3. 3.INSERM-UPMC UMR 1166 Hôpital de la PitiéParisFrance
  4. 4.AP-HP, Hôpitaux Universitaires Paris Ile-de-France Ouest, Site Ambroise ParéService de Biochimie et Génétique MoléculaireBoulogne-BillancourtFrance
  5. 5.Université Versailles Saint-Quentin-en-Yvelines, UFR des Sciences de la Santé Simone VeilMontigny-Le-BretonneuxFrance
  6. 6.Faculté de Médecine Paris 7Université Denis DiderotParisFrance
  7. 7.Département de GénétiqueAP-HP, CHU Xavier BichatParisFrance

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