title: Anti-PCSK9 therapies for the treatment of hypercholesterolemia.
abstract: BACKGROUND
  Proprotein convertase subtilisin kexin type 9 (PCSK9), a serine protease that binds to the low density lipoprotein (LDL) receptor promoting its degradation, is an important regulator of LDL metabolism. PCSK9 'gain-of-function' mutations are rare and cause high plasma LDL-cholesterol and increase atherosclerotic cardiovascular disease, whereas more common 'loss-of-function' mutations cause low LDL-cholesterol and atheroprotection. PCSK9 is a novel, attractive and viable therapeutic target for the treatment of hypercholesterolemia, with human studies using a variety of anti-PCSK9 therapies underway.
  
  
  METHODS
  This review summarizes the latest findings in clinical trials of PCSK9 inhibitors, including antibodies, gene silencing and small peptides.
  
  
  CONCLUSIONS
  PCSK9 inhibition would appear to be an effective strategy for lowering plasma LDL-cholesterol and enhancing the LDL-cholesterol lowering ability of statins in patients with familial hypercholesterolemia, patients with refractory hypercholesterolemia at high risk of cardiovascular disease and patients with severe hypercholesterolemia who are not at target or are intolerant of statins, with a variety of anti-PCSK9 therapies in clinical trials.
authors.affiliation: Royal Perth Hospital, Department of Core Clinical Pathology & Biochemistry, PathWest Laboratory Medicine WA, Perth, Western Australia.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Hooper
authors.forename: John R
authors.initials: JR
authors.lastname: Burnett
mesh_terms: D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000037:antagonists & inhibitors*; D012697:Serine Endopeptidases
chemical_list: D000924:Anticholesteremic Agents; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases