A pilot study of ex vivo gene therapy for homozygous familial hypercholesterolaemia
@article{Grossman1995APS, title={A pilot study of ex vivo gene therapy for homozygous familial hypercholesterolaemia}, author={Mariann Grossman and Daniel J. Rader and David W M Muller and Daniel M. Kolansky and Karen Kozarsky and Bernard J. Clark and Evan A. Stein and Paul J. Lupien and H. Bryan Jr. Brewer and Steven E Raper and James M. Wilson}, journal={Nature Medicine}, year={1995}, volume={1}, pages={1148-1154} }
The outcome of the first pilot study of liver-directed gene therapy is reported here. Five patients with homozygous familial hypercholesterolaemia (FH) ranging in age from 7 to 41 years were enrolled; each patient tolerated the procedure well without significant complications. Transgene expression was detected in a limited number of hepatocytes of liver tissue harvested four months after gene transfer from all five patients. Significant and prolonged reductions in low density lipoprotein (LDL…
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Recent Developments in Gene Therapy for Homozygous Familial Hypercholesterolemia
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A recombinant adeno-associated virus vector carrying a low-density lipoprotein receptor (LDLR) transgene which has recently entered phase 1/2a testing is discussed and a summary of key gene therapy approaches for HoFH in pre-clinical development is included, including RNA silencing of HMG-CoA reductase and induced pluripotent stem cell transplant therapy.
LDLR-Gene therapy for familial hypercholesterolaemia: problems, progress, and perspectives
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Progress made in the 18 years since the first ex vivo clinical trial for gene therapy of FH is reviewed, with emphasis on the development, design, performance and limitations of viral based gene transfer vectors used in studies to ameliorate the effects of LDLR deficiency.
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The genetic basis of the FH disease is reviewed, paying special attention to the severe HoFH as well as the challenges in its diagnosis and clinical management, and the current therapies for this disease are discussed.
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This work evaluated an alternative strategy of ectopic expression in the liver of the very low density lipoprotein (VLDL) receptor, which is homologous to the LDL receptor but has a different pattern of expression.
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Systemic gene therapy for cardiovascular disease.
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A gene therapy protocol for FH using AAV2, AAV9 and lentiviral vectors is developed and safety and efficacy in LDL receptor deficient Watanabe Heritable Hyperlipidemic rabbits are tested and it is shown that LV-LDLR produced a significant long-lasting decrease in total serum cholesterol.
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