Safety and feasibility of liver-directed ex vivo gene therapy for homozygous familial hypercholesterolemia

Annals of Surgery
S E RaperJ M Wilson

Abstract

The purpose of this report was to provide detailed information on the safety and feasibility of surgical procedures associated with the first ex vivo liver-directed gene therapy trial for the treatment of vivo gene therapy for homozygous familial hypercholesterolemia (FH). Familial hypercholesterolemia is an autosomal dominant disease in which the gene encoding the low density lipoprotein receptor is defective. Patients homozygous for this mutation have extraordinarily high levels of cholesterol and accelerated atherosclerosis and die prematurely of myocardial infarction. The concept of liver-directed gene therapy was based on the report of normalization of cholesterol levels by orthotopic cardiac/liver transplant in a child with homozygous FH. Five patients with homozygous FH were selected for inclusion in this trial. The patients underwent hepatic resection and placement of a portal venous catheter. Primary hepatocytes cultures were prepared from the resected liver and transduced with a recombinant retrovirus encoding the gene for the human low density lipoprotein receptor. The genetically modified cells were then transplanted into the liver through the portal venous catheter. Numerous clinical, laboratory, and radiologic par...Continue Reading

References

Apr 11, 1992·Human Gene Therapy·J M WilsonJ G Thoene
Nov 1, 1991·Somatic Cell and Molecular Genetics·M GrossmanJ M Wilson
Nov 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·J M WilsonJ R Chowdhury
Apr 4, 1986·Science·M S Brown, J L Goldstein

❮ Previous
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Citations

Jan 1, 1997·International Journal of Clinical & Laboratory Research·D J Rader
Dec 10, 2003·Current Atherosclerosis Reports·Michael H Davidson
Dec 21, 2000·Current Atherosclerosis Reports·D J Rader, U J Tietge
Jan 27, 1999·Atherosclerosis·C R SirtoriG Franceschini
Dec 31, 2003·Biomaterials·Daniel Palmes, Hans-Ullrich Spiegel
Apr 12, 2002·Journal of Hepatology·Jurgen SeppenRonald P J Oude Elferink
May 30, 2001·Advanced Drug Delivery Reviews·Y KagawaH Endo
May 15, 1998·The New England Journal of Medicine·J R Lake
Sep 10, 1996·Human Gene Therapy·G RossB R Smith
Oct 13, 2006·Current Opinion in Gastroenterology·R J Fontana, L G Quallich
Aug 18, 2005·Cardiology in Review·Tanaz Kermani, William H Frishman
Jul 9, 2004·Transplantation·Simon P Horslen, Ira J Fox
Aug 24, 2006·Transplantation·Robert A Fisher, Stephen C Strom
Jun 5, 2007·Pediatric Dermatology·Gomathy SethuramanVinod K Sharma
Dec 13, 2006·Medical Principles and Practice : International Journal of the Kuwait University, Health Science Centre·J P SelvanR Jebaraj
Feb 15, 1997·The Journal of Clinical Investigation·H M KarpoffY Fong
Nov 6, 2004·Cell Structure and Function·Seiji TakashimaToshio Nikaido
Dec 31, 2010·Vascular Health and Risk Management·Mohammad Hassan Nemati, Behrooz Astaneh
Jul 1, 2008·Regenerative Medicine·Jörg C GerlachJohn F Patzer Ii
Jul 28, 2015·Expert Review of Gastroenterology & Hepatology·David Christopher Bartlett, Philip N Newsome
Jul 5, 2005·Expert Opinion on Investigational Drugs·J WuM A Zern
Feb 17, 2010·Molecular Genetics and Metabolism·Jochen Meyburg, Georg F Hoffmann
Nov 6, 2004·The Australasian Journal of Dermatology·Mignon Moyle, Bruce Tate
Dec 22, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Ina RittelmeyerMichael Ott
Feb 1, 2011·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Eva TörökJoerg M Pollok
Oct 12, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Ralf BahdeSanjeev Gupta
Nov 6, 2003·The American Journal of Medicine·Thomas A RatkoKarl A Matuszewski
Sep 11, 1999·The Journal of Laboratory and Clinical Medicine·M Belalcazar, L Chan
Feb 1, 1997·Journal of Pediatric Surgery·R A CusickJ P Vacanti
Apr 9, 1998·The Surgical Clinics of North America·J F Valente, J W Alexander
Aug 13, 2015·Medical Journal, Armed Forces India·Vikas Pathania, Arpitha Yadav
Feb 13, 1997·Biochemical and Biophysical Research Communications·W XiongL Chao
Jan 21, 2000·Preventive Medicine·R R WilliamsS C Hunt
Nov 21, 2014·Current Atherosclerosis Reports·Claudia Stefanutti, Gilbert R Thompson
Apr 20, 2004·Molecular Therapy : the Journal of the American Society of Gene Therapy·Hanna M KankkonenSeppo Ylä-Herttuala
Jan 8, 2010·Cell Transplantation·Jochen MeyburgJens-Peter Schenk
May 17, 2006·Cell Transplantation·Hiroyuki KugeYoshiyuki Nakajima
Mar 18, 2006·Nature Reviews. Genetics·Timothy P O'Connor, Ronald G Crystal

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