Homozygous autosomal dominant hypercholesterolaemia: prevalence, diagnosis, and current and future treatment...

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.

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.

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.