Trial reportAnnals of surgery1996
Safety and feasibility of liver-directed ex vivo gene therapy for homozygous familial hypercholesterolemia.
Trial report in Annals of surgery, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 112 citations in OpenAlex.
- The promising novel therapies for familial hypercholesterolemia.Journal of clinical laboratory analysis · 2022Pooled it
- A pilot study of ex vivo gene therapy for homozygous familial hypercholesterolaemia.Nature medicine · 1995Trial
- Progress in Gene Therapy for Hereditary Tyrosinemia Type 1.Pharmaceutics · 2025Review
- Novel vectors and approaches for gene therapy in liver diseases.JHEP reports : innovation in hepatology · 2021Review
- Function and Immunogenicity of Gene-corrected iPSC-derived Hepatocyte-Like Cells in Restoring Low Density Lipoprotein Uptake in Homozygous Familial Hypercholesterolemia.Scientific reports · 2019Article
- Gene therapy for monogenic liver diseases: clinical successes, current challenges and future prospects.Journal of inherited metabolic disease · 2017Review
- A case of familial hypercholesterolaemia Type IIa presenting with tuberous xanthomas.Medical journal, Armed Forces India · 2015Article
- Improvement of Infusion Process in Cell Transplantation: Effect of Shear Stress on Hepatocyte Viability Under Horizontal and Vertical Syringe Orientation.Cell medicine · 2015Article
- Lipoprotein apheresis in the management of familial hypercholesterolaemia: historical perspective and recent advances.Current atherosclerosis reports · 2015Review
- Endothelin-1 receptor A blocker darusentan decreases hepatic changes and improves liver repopulation after cell transplantation in rats.Hepatology (Baltimore, Md.) · 2014Article
- Optimal management of familial hypercholesterolemia: treatment and management strategies.Vascular health and risk management · 2010Review
- Hepatocyte transplantation-induced liver inflammation is driven by cytokines-chemokines associated with neutrophils and Kupffer cells.Gastroenterology · 2009Article
- Biologic therapies for dyslipidemia.Current atherosclerosis reports · 2004Review
- Hepatocyte transplantation for inborn errors of metabolism.Journal of inherited metabolic disease · 2004Review
- Transplantation of primary and reversibly immortalized human liver cells and other gene therapies in acute liver failure and decompensated chronic liver disease.World journal of gastroenterology · 2000Article
- Gene therapy for dyslipidemia: clinical prospects.Current atherosclerosis reports · 1999Review
- Developing adenoviral-mediated in vivo gene therapy for ornithine transcarbamylase deficiency.Journal of inherited metabolic disease · 1998Article
- Absence of the inferior mesenteric vein.Annals of surgery · 1997Article
- Prevention of hepatic tumor metastases in rats with herpes viral vaccines and gamma-interferon.The Journal of clinical investigation · 1997Article
Corrections and comments
- Commented on by
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe 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). SUMMARY BACKGROUND DATA: 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.
methodsFive 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.
resultsNumerous clinical, laboratory, and radiologic parameters were analyzed. Elevations of the hepatic transaminases and leukocyte counts and a decline in hematocrit count were noted. Transient elevations of the portal pressure were observed during cell infusion. No major perioperative morbidity--specifically, myocardial infarct, perioperative hemorrhage, or portal vein thrombosis--or death occurred as a result of this protocol.
conclusionLiver-directed ex vivo gene therapy can be accomplished safely in humans and is appropriate for selected patients.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.