Targeting Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9): A New Promising Approach for the Management of Hypercholesterolemia

Abstract

Statins remain the standard of care for low-density lipoprotein cholesterol (LDL-C) lowering and reduction of cardiovascular risk. However, there are still cases in which patients fail to achieve the desired LDL-C goals or are intolerant to statins due to side effects (mostly myalgias). Thus, extensive research is being conducted to identify new LDL-C lowering drugs with a favorable side effect profile, which (used alone or in combination with statin therapy) would be able to produce significant LDL-C reductions and decrease cardiovascular risk [1,2].Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease, which is expressed mainly in the liver but may also be found in the intestine and kidneys. The human PCSK9 gene is located in the human chromosome 1p32.3 and encodes a 692-amino acid inactive glycoprotein, which undergoes an intramolecular self-catalytic cleavage in the endoplasmic reticulum [3]. trial, alirocumab, administered on top of maximally tolerated dose of statin, alone or in combination with other lipid-lowering agents, caused an additional 61.9% reduction in LDL-C levels, as compared with placebo [18,19].