Effect of a Monoclonal Antibody to PCSK9 on LDL Cholesterol

A monoclonal antibody to PCSK9 was studied in two single-dose trials in healthy volunteers and one multiple-dose trial in patients with familial or nonfamilial hypercholesterolemia. In all three groups, the antibody reduced levels of LDL cholesterol. In 2003, Abifadel and colleagues 1 described two families with autosomal dominant hypercholesterolemia that was associated with gain-of-function mutations in proprotein convertase subtilisin/kexin 9 (PCSK9), one of the serine proteases. These patients had high plasma levels of low-density lipoprotein (LDL) cholesterol, which was associated with an increased incidence of coronary heart disease. Shortly thereafter, studies of animal models identified a role for PCSK9 in the post-translational regulation of LDL-receptor activity. 2 , 3 PCSK9, which is synthesized primarily in the liver, enters the circulation, where it binds to hepatic LDL receptors and targets them for degradation. This process reduces the capacity of the . . .