title: Pharmacogenetics in the Development of Lipid Lowering Medications: Lomitapide & Mipomersen in Clinical Practice.
abstract: BACKGROUND
  The familial hypercholesterolemias (FH) are a group of undertreated genetically inherited disorders of lipid metabolism that lead to severely elevated cholesterol levels and early onset cardiovascular disease. Aggressive lifestyle modifications and lipid-lowering medications such as statins and bile acid sequestrants are the backbone of current treatment. Despite these interventions, homozygous FH (HoFH) patients are unable to reach LDL-C targets and remain at significantly increased risk of cardiovascular disease. Recently, two novel lipid-lowering medications, lomitapide and mipomersen, have been approved for the treatment of HoFH.
  
  
  METHODS
  We present two patients with HoFH who have been unable to reach target LDL-C goals on standard therapy. Patient A is a 41-year-old male and patient B is a 64-year-old female, both of whom have complex histories of multi-vessel coronary artery disease. In attempt to improve their LDL-C levels and lower their cardiovascular risk, lomitapide and mipomersen were initiated in patient A and B, respectively.
  
  
  CONCLUSIONS
  Through inhibition of the microsomal triglyceride transfer protein, lomitapide prevents the formation of triglyceride rich lipoproteins. Mipomersen is an antisense oligonucleotide that inhibits the translation of apolipoprotein B-100. Both medications employ novel mechanisms developed through advances in pharmacogenetic technology and achieve unprecedented LDL-C reductions.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Marbach
authors.forename: Jhapat
authors.initials: J
authors.lastname: Thapa
authors.forename: Edward
authors.initials: E
authors.lastname: Goldenberg
authors.forename: Danielle
authors.initials: D
authors.lastname: Duffy
mesh_terms: D000328:Adult; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009841:Oligonucleotides / Q000627:therapeutic use*; D010597:Pharmacogenetics
chemical_list: D000924:Anticholesteremic Agents; C473731:BMS201038; D001562:Benzimidazoles; D008078:Cholesterol, LDL; D009841:Oligonucleotides; C524142:mipomersen