Anti-PCSK9 Vaccines - An Emerging Therapeutic Innovative Game Changer in Dyslipidemia and Beyond

Proprotein convertase subtilisin/kexin type 9 serine protease (PCSK9) regulates the cholesterol metabolism by genetic mechanism mediating the LDL receptor degradation. Gain of the functions of the PCSK9 variants resulted in high level of LDL-cholesterol and loss of function in low level of the LDL-cholesterol level. The low level of LDL-cholesterol was associated with significant decrease in coronary artery disease. The genetic insight of lipid homeostasis and complex molecular biochemistry triggered a domain of active pharmacological research with prospect of introducing paradigm shift in primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD) in group of non-responders to anti-cholesterol treatment. The result has been the discovery of the PCSK9 inhibitors and vaccines. The former got the statutory approval by Federal Drug Administration (FDA) in conditions namely patients with heterozygous familial hypercholesterolemia (FH), individuals with ASCVD requiring further lowering of LDL-cholesterol levels. This has also important role in statin-intolerant patients. The various international guidelines have put the concept of the therapeutic approach in acute coronary syndrome (ACS) specially in high risk post-MI patients. However the present article will focus more on the PCSK9 vaccine and the encouraging evidences of its pleotropic effects in treatment of chronic clinical conditions and cancer. There are few challenges which need to be further explored especially considering the cost-benefit ratio. There is also the need of further research focusing on the expansion of the indications.