title: Mipomersen, an antisense apolipoprotein B synthesis inhibitor.
abstract: BACKGROUND
  mipomersen is a second-generation antisense oligonucleotide (ASO) targeted to human apolipoprotein (apo) B-100, a large protein synthesized by the liver that plays a fundamental role in human lipoprotein metabolism. Mipomersen predominantly distributes to the liver and decreases the production of apoB-100, the primary structural protein of the atherogenic lipoproteins including low density lipoprotein (LDL), thereby reducing plasma LDL-cholesterol and apoB-100 concentrations.
  
  
  METHODS
  the mode of action, preclinical development and clinical trials of mipomersen, an antisense apoB synthesis inhibitor. The paper provides an understanding of the pharmacokinetic and pharmacodynamic characteristics of mipomersen and insight into its clinical efficacy and safety. In clinical trials, mipomersen produced dose-dependent and prolonged reductions in LDL-cholesterol and other apoB-containing lipoproteins, including lipoprotein (a) [Lp(a)] in healthy volunteers and in patients with mild to moderate hypercholesterolemia. Mipomersen has been shown to decrease apoB, LDL-cholesterol and Lp(a) in patients with heterozygous and homozygous familial hypercholesterolemia on maximally tolerated lipid-lowering therapy.
  
  
  CONCLUSIONS
  mipomersen shows promise as an adjunctive agent by reducing apoB-containing lipoproteins in patients at high risk of atherosclerotic cardiovascular disease who are not at target or are intolerant of statins. Although the short-term efficacy and safety of mipomersen has been established, concern exists regarding the long-term potential for hepatic steatosis with this ASO.
authors.affiliation: Royal Perth Hospital, Department of Core Clinical Pathology & Biochemistry, PathWest Laboratory Medicine, Perth, Western Australia.
authors.forename: Damon A
authors.initials: DA
authors.lastname: Bell
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Hooper
authors.forename: John R
authors.initials: JR
authors.lastname: Burnett
mesh_terms: D053299:Apolipoprotein B-100 / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D008078:Cholesterol, LDL / Q000097:blood / Q000378:metabolism; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy; D006949:Hyperlipidemias / Q000188:drug therapy*; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy; D058990:Molecular Targeted Therapy; D009841:Oligonucleotides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D053299:Apolipoprotein B-100; D008078:Cholesterol, LDL; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; C524142:mipomersen