A review of gene- and cell-based therapies for familial hypercholesterolemia

Publication date: Available online 22 March 2019Source: Pharmacological ResearchAuthor(s): Saeideh Hajighasemi, Armita Mahdavi Gorabi, Vanessa Bianconi, Matteo Pirro, Maciej Banach, Hossein Ahmadi tafti, Željko Reiner, Amirhossein SahebkarAbstractFamilial hypercholesterolemia (FH) is a genetic autosomal dominant disorder caused by an impaired receptor-mediated low-density lipoprotein (LDL) removal from the circulation, mainly due to disruptive autosomal co-dominant mutations in the LDL receptor (LDLr) gene, but also less frequently in the apolipoprotein B100 (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. A rare form of autosomal recessive FH has been also described due to LDLr adaptor protein 1 (LDLRAP1) gene mutations. FH is characterized by very high levels of plasma LDL cholesterol associated with the high incidence of premature atherosclerotic cardiovascular disease (CVD). Despite heterozygous FH (HeFH) patients are still poorly recognized and treated, there is today a large availability of drugs (i.e., statins, ezetimibe and PCSK9 inhibitors) allowing theoretically the normalization of plasma LDL cholesterol levels in this population. Homozygous FH patients (HoFH) have a more severe form of FH, characterized by low responsiveness to the conventional lipid-lowering treatment and often associated with unfavorable prognosis in the young age. Inspired by promising outcomes obtained by orthotopic liver transplantation (OLT), scientists are investigat...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research