title: Strategies for proprotein convertase subtilisin kexin 9 modulation: a perspective on recent patents.
abstract: BACKGROUND
  Proprotein convertase subtilisin kexin 9 (PCSK9) is a new actor discovered in 2003 that is implicated in autosomal dominant hypercholesterolemia, cholesterol homeostasis and coronary heart disease. It has been shown to degrade the low-density lipoprotein (LDL) receptor independently of its catalytic activity. Several pharmacological strategies to reduce PCSK9 are being thoroughly investigated.
  
  
  METHODS
  This article reviews all different strategies that are presently pursued to modulate the functional activity of PCSK9 which is a prime target for controlling LDL-cholesterol. It also provides a briefing of all the patents up to July 2010 from various organizations including pharmaceutical companies and academic institutions that have been submitted and/or approved.
  
  
  RESULTS
  This review is addressed to researchers from academia and pharmaceutical companies who are engaged in PCSK9 research/cholesterol regulation and in the development of cholesterol lowering drugs. Readers will gain an up-to-date overview of the different strategies that have been investigated to reduce PCSK9 including antisense technology and specific antibodies.
  
  
  CONCLUSIONS
  Clinical trials have been launched using RNA interference approaches to reduce PCSK9 expression or specific antibodies targeting and inhibiting PCSK9 interaction with the LDL receptor. They constitute very promising approaches to reducing cholesterol levels and coronary heart disease.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Inserm UMR698, Hemostasis, Bio-Engineering and Cardiovascular Remodelling, Hôpital Bichat-Claude Bernard, 46 Rue Henri Huchard, 75877 Paris Cedex 18, France. marianne.abi-fadel@inserm.fr
authors.forename: Marianne
authors.initials: M
authors.lastname: Abifadel
authors.forename: Jihane
authors.initials: J
authors.lastname: Pakradouni
authors.forename: Matthieu
authors.initials: M
authors.lastname: Collin
authors.forename: Marie-Elisabeth
authors.initials: ME
authors.lastname: Samson-Bouma
authors.forename: Mathilde
authors.initials: M
authors.lastname: Varret
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Rabès
authors.forename: Catherine
authors.initials: C
authors.lastname: Boileau
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D003327:Coronary Disease / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control / Q000628:therapy; D016503:Drug Delivery Systems; D015195:Drug Design; D005786:Gene Expression Regulation; D006801:Humans; D006937:Hypercholesterolemia / Q000503:physiopathology* / Q000628:therapy; D010330:Patents as Topic; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D034622:RNA Interference; D012697:Serine Endopeptidases / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
chemical_list: D002784:Cholesterol; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases