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Effect of a Monoclonal Antibody to PCSK9 on LDL Cholesterol
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Effect of a Monoclonal Antibody to PCSK9 on LDL Cholesterol
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Effect of a Monoclonal Antibody to PCSK9 on LDL Cholesterol
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Journal Article
Effect of a Monoclonal Antibody to PCSK9 on LDL Cholesterol
2012
Overview
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 . . .
Publisher
Massachusetts Medical Society
Subject
/ Antibodies, Monoclonal - administration & dosage
/ Antibodies, Monoclonal - adverse effects
/ Anticholesteremic Agents - administration & dosage
/ Anticholesteremic Agents - adverse effects
/ Anticholesteremic Agents - therapeutic use
/ Biological and medical sciences
/ Dose-Response Relationship, Drug
/ Female
/ Heptanoic Acids - therapeutic use
/ Humans
/ Hypercholesterolemia - drug therapy
/ Hypercholesterolemia - metabolism
/ Hyperlipoproteinemia Type II - drug therapy
/ Hyperlipoproteinemia Type II - metabolism
/ Kexin
/ Male
/ Proprotein Convertases - antagonists & inhibitors
/ Proprotein Convertases - immunology
/ Proprotein Convertases - metabolism
/ Receptors, LDL - drug effects
/ Serine
/ Serine Endopeptidases - immunology
