Journal
DRUG DESIGN DEVELOPMENT AND THERAPY
Volume 7, Issue -, Pages 1135-1148Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/DDDT.S36984
Keywords
PCSK9; LDLR; LDL-cholesterol; lipoproteins; coronary heart disease; inhibitors; monoclonal antibody therapy
Categories
Funding
- Canadian Institutes of Health Research (Institute of Nutrition, Metabolism, and Diabetes)
- Fonds de recherche du Quebec-Sante
- Heart and Stroke Foundation of Canada
- Montreal Heart Institute Foundation
Ask authors/readers for more resources
Proprotein convertase subtilisin/kexin type 9 (PCSK9) directly binds to the epidermal growth factor-like repeat A domain of low-density lipoprotein receptor and induces its degradation, thereby controlling circulating low-density lipoprotein cholesterol (LDL-C) concentration. Heterozygous loss-of-function mutations in PCSK9 can decrease the incidence of coronary heart disease by up to 88%, owing to lifelong reduction of LDL-C. Moreover, two subjects with PCSK9 loss-of-function mutations on both alleles, resulting in a total absence of functional PCSK9, were found to have extremely low circulating LDL-C levels without other apparent abnormalities. Accordingly, PCSK9 could represent a safe and effective pharmacological target to increase clearance of LDL-C and to reduce the risk of coronary heart disease. Recent clinical trials using anti-PCSK9 monoclonal antibodies that block the PCSK9: low-density lipoprotein receptor interaction were shown to considerably reduce LDL-C levels by up to 65% when given alone and by up to 72% in patients already receiving statin therapy. In this review, we will discuss how major scientific breakthroughs in PCSK9 cell biology have led to the development of new and forthcoming LDL-C-lowering pharmacological agents.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available