title: Anti-sense oligonucleotide therapies for the treatment of hyperlipidaemia.
abstract: Anti-sense oligonucleotide (ASO) therapies are a new development in clinical pharmacology offering greater specificity compared to small molecule inhibitors and the ability to target intracellular process' not susceptible to antibody-based therapies.
  
  
  
  This article reviews the chemical biology of ASOs and related RNA therapeutics. It then reviews the data on their use to treat hyperlipidaemia. Data on mipomersen - an ASO to apolipoprotein B-100(apoB) licensed for treatment of homozygous familial hypercholesterolaemia (FH) is presented. Few effective therapies are available to reduce atehrogenic lipoprotein (a) levels. An ASO therapy to apolipoprotein(a) (ISIS Apo(a)Rx) specifically reduced lipoprotein (a) levels by up to 78%. Treatment options for patients with familial chylomicronaemia syndrome (lipoprotein lipase deficiency; LPLD) or lipodystrophies are highly limited and often inadequate. Volanesorsen, an ASO to apolipoprotein C-3, shows promise in the treatment of LPLD and severe hypertriglyceridaemia as it increases clearance of triglyceride-rich lipoproteins and can normalise triglycerides in these patients.
  
  
  
  The uptake of the novel ASO therapies is likely to be limited to selected niche groups or orphan diseases. These will include homozygous FH, severe heterozygous FH for mipomersen; LPLD deficiency and lipodystrophy syndromes for volanesorsen and treatment of patients with high elevated Lp(a) levels.
authors.affiliation: a Department of Metabolic Medicine/Chemical Pathology , Guy's and St Thomas' Hospitals , London , UK.
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Wierzbicki
authors.affiliation: b Consultant in Metabolic Medicine/Chemical Pathology , Lister Hospital , Stevenage , UK.
authors.forename: Adie
authors.initials: A
authors.lastname: Viljoen
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D053299:Apolipoprotein B-100 / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D008072:Hyperlipoproteinemia Type I / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D015228:Hypertriglyceridemia / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D009841:Oligonucleotides / Q000627:therapeutic use; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: C569471:APOB protein, human; D000924:Anticholesteremic Agents; D053299:Apolipoprotein B-100; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; C524142:mipomersen
keywords: Familial hypercholesterolaemia; angiopoietin-like protein 3 (ANGPTL3); antisense oligonucleotide; familial chylomcronaemia syndrome; lipodystrophy; lipoprotein lipase deficiency; lipoprotein(a); treatment