Homozygous autosomal dominant hypercholesterolaemia: prevalence, diagnosis, and current and future treatment perspectives. Issue 3 (June 2015)

• Record Type: Journal Article
• Authors: Sjouke, Barbara; Hovingh, G. Kees; Kastelein, John J.P.; Stefanutti, Claudia
• Is Part Of: Current opinion in lipidology. Volume 26:Issue 3(2015:Jun.)
• Publication Date: 2015-06
• Subjects: autosomal dominant hypercholesterolaemia -- HDL enhancers -- lipoprotein apheresis -- mipomersen -- microsomal triglyceride transfer protein inhibitors -- proprotein convertase subtilisin-kexin type 9 inhibitors; Lipids -- Periodicals; 572.574
• DOI: 10.1097/MOL.0000000000000179
• Languages: English
• ISSNs: 1473-6535

Abstract

Abstract : Purpose of review: Homozygous autosomal dominant hypercholesterolemia (hoADH) is a rare genetic disorder caused by mutations in LDL receptor, apolipoprotein B, and/or proprotein convertase subtilisin-kexin type 9. Both the genetic mutations and the clinical phenotype vary largely among individual patients, but patients with hoADH are typically characterized by extremely elevated LDL-cholesterol (LDL-C) levels, and a very high-risk for premature cardiovascular disease. Current lipid-lowering therapies include bile acid sequestrants, statins, and ezetimibe. To further decrease LDL-C levels in hoADH, lipoprotein apheresis is recommended, but this therapy is not available in all countries. Recent findings: Recently, the microsomal triglyceride transfer protein inhibitor lomitapide and the RNA antisense inhibitor of apolipoprotein B mipomersen were approved by the Food and Drug Administration/European Medicine Agency and the Food and Drug Administration, respectively. Several other LDL-C-lowering strategies and therapeutics targeting the HDL-C pathway are currently in the clinical stage of development. Summary: Novel therapies have been introduced for LDL-C-lowering and innovative drug candidates for HDL-C modulation for the treatment of hoADH. Here, we review the current available literature on the prevalence, diagnosis, and therapeutic strategies for hoADH.