Progress and prospects of biological approaches targeting PCSK9 for cholesterol-lowering, from molecular mechanism to clinical efficacy.

Introduction: Cardiovascular disorders are one of the leading causes of mortality and morbidity worldwide. Recent advances showed a promising role of proprotein convertase subtilisin/kexin type 9 (PCSK9) as a critical player in regulating plasma LDL levels and lipid metabolism.

Areas Covered: This review addresses the molecular functions of PCSK9 with a vision on the clinical progress of utilizing monoclonal antibodies and other biological approaches to block PCSK9 activity. The successful clinical trials with monoclonal antibodies are reviewed. Recent advances in (pre)clinical trials of other biological approaches, such as small interfering RNAs, are also discussed.

Expert Opinion: Discovery of PCSK9 and clinical use of its inhibitors to manage lipid metabolism is a step forward in hypolipidaemic therapy. A better understanding of the molecular activity of PCSK9 can help to identify new approaches in the inhibition of PCSK9 expression/activity. Whether if PCSK9 plays a role in other cardiometabolic conditions may provide grounds for further development of therapies.