EX VIVO GENE THERAPY FOR FAMILIAL HYPERCHOLESTEROLEMIA

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Familial Hypercholesterolemia (FH) is an inherited disease of low density lipoprotein (LDL) receptor expression that has emerged as an important clinical model for the development of gene therapies directed to the liver. Patients who are homozygous for this disease have severe hypercholesterolemia and die of coronary artery disease in childhood. The success of orthotopic liver transplantation in correcting the underlying metablic defect in FH confirms that the hepatocyte is an appropriate target for somatic gene transfer. This study demonstrates the feasiblity of engrafting limited numbers of retrovirus-transduced hepatocytes without morbidity and achieving persistent gene expression lasting at least four months after gene therapy. The variable metabolic responses observed following low level genetic reconstitution in the five patients studied thus far precludes a broader application of liver-directed gene therapy without modifications that consistently produce substantially greater gene transfer.