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

Nature Genetics volume 6, pages 335–341 (1994)Cite this article

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.

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Author notes

  1. Mariann Grossman, Steven E. Raper, Karen Kozarsky, John F. Engelhardt & James M. Wilson

    Present address: Institute for Human Gene Therapy, University of Pennsylvania, Wistar Institute, Room 204, 3601 Spruce Street, Philadelphia, Pennsylvania, 19104-4268, USA

Authors and Affiliations

  1. Departments of Internal Medicine, Surgery, and Biological Chemistry, The University of Michigan Medical Center, Ann Arbor, Michigan, 48109-0366, USA

    Mariann Grossman, Steven E. Raper, Karen Kozarsky, John F. Engelhardt, David Muller & James M. Wilson

  2. Division of Lipid Metabolism and Preventive Atherosclerosis, The Christ Hospital Cardiovascular Research Center,

    Evan A. Stein

  3. Medical Research Laboratories, Cincinnati, Ohio, 45219, USA

    Evan A. Stein

  4. Lipid Research Center, Laval University Hospital Medical Research Center, Québec, G1V4G2, Canada

    Paul J. Lupien

Authors
  1. Mariann Grossman
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  2. Steven E. Raper
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  3. Karen Kozarsky
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  4. Evan A. Stein
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  5. John F. Engelhardt
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  6. David Muller
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  7. Paul J. Lupien
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  8. James M. Wilson
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Grossman, M., Raper, S., Kozarsky, K. et al. Successful ex vivo gene therapy directed to liver in a patient with familial hypercholesterolaemia. Nat Genet 6, 335–341 (1994). https://doi.org/10.1038/ng0494-335

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