Successful ex vivo gene therapy directed to liver in a patient with familial hypercholesterolaemia

Nat Genet. 1994 Apr;6(4):335-41. doi: 10.1038/ng0494-335.

Abstract

An ex vivo approach to gene therapy for familial hypercholesterolaemia (FH) has been developed in which the recipient is transplanted with autologous hepatocytes that are genetically corrected with recombinant retroviruses carrying the LDL receptor. We describe the treatment of a 29 year old woman with homozygous FH by ex vivo gene therapy directed to liver. She tolerated the procedures well and in situ hybridization of liver tissue four months after therapy revealed evidence for engraftment of transgene expressing cells. The patient's LDL/HDL ratio declined from 10-13 before gene therapy to 5-8 following gene therapy, improvements which have remained stable for the duration of the treatment (18 months). This represents the first report of human gene therapy in which stable correction of a therapeutic endpoint has been achieved.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Biopsy
  • Cells, Cultured / transplantation*
  • Combined Modality Therapy
  • Coronary Artery Bypass
  • Coronary Disease / etiology
  • Coronary Disease / surgery
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation / drug effects
  • Genes, Synthetic
  • Genetic Therapy* / methods
  • Genetic Vectors
  • Humans
  • Hyperlipoproteinemia Type II / blood
  • Hyperlipoproteinemia Type II / complications
  • Hyperlipoproteinemia Type II / drug therapy
  • Hyperlipoproteinemia Type II / pathology
  • Hyperlipoproteinemia Type II / therapy*
  • In Situ Hybridization, Fluorescence
  • Lipoproteins, HDL / blood
  • Lipoproteins, LDL / blood
  • Liver* / drug effects
  • Liver* / metabolism
  • Liver* / pathology
  • Lovastatin / pharmacology
  • Lovastatin / therapeutic use
  • Receptors, LDL / biosynthesis
  • Receptors, LDL / deficiency
  • Receptors, LDL / genetics*
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / therapeutic use*
  • Safety
  • Up-Regulation / drug effects

Substances

  • Lipoproteins, HDL
  • Lipoproteins, LDL
  • Receptors, LDL
  • Recombinant Proteins
  • Lovastatin