PCSK9 inhibitors as a new modality for treating dyslipidemia

Abstract

Managing dyslipidemia is a crucial approach to reducing the likelihood of developing atherosclerotic cardiovascular disease. The Food and Drug Administration has approved Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors for the treatment of dyslipidemia. This study provides a comprehensive overview of the latest information on developing medicines that target PCSK9 to decrease cholesterol levels. PCSK9 attaches to the low-density lipoprotein (LDL) receptor, leading to the receptor\'s breakdown in the lysosome. Individuals with gain-of-function mutations in PCSK9 exhibit reduced expression of LDL receptors on the surface of hepatocytes, leading to elevated levels of LDL cholesterol (LDL-C). Conversely, mutations that cause PCSK9 to lose its activity are linked to reduced levels of LDL-C and a notably decreased lifetime risk of cardiovascular disease.Monoclonal antibodies that target PCSK9, such as evolocumab and alirocumab, were created and found to significantly decrease LDL-C by as much as 60% in various populations, whether used alone or in conjunction with statins. These findings have expanded the range of pharmaceutical methods available for managing the remaining cardiovascular risk associated with LDL-C. PCSK9 antibodies exhibit a low risk of adverse effects. Emerging strategies for blocking PCSK9 show great potential. Novel PCSK9 inhibitors have been researched and are being implemented for therapeutic applications. Additional clinical trials are necessary to yield valuable data regarding the effectiveness of these substances and their function in the treatment of dyslipidemia.