PCSK9 inhibitors are a new type of cholesterol-lowering drug. Those inhibitors are monoclonal antibodies that target and inactivate a liver protein, known as proprotein convertase subtilisin kexin 9. Knocking out this protein, the amount of harmful LDL cholesterol circulating in the bloodstream reduces dramatically. This LDL reduction translates into fewer strokes, heart attacks and other problems related to cholesterol-clogged arteries, once arteries becomes healthier.
Premature cardiovascular disorders and associated mortality are significatively related to heterozygous familial hypercholesterolaemia (HeFH), which is one of the most frequent genetic disease. The role of PCSK9 in such and similar health issues is regulation of hepatic LDL receptor action; blocking PCSK9 binding to the LDLR with a monoclonal antibody has been accepted as an eficient LDL lowering.
PCSK9 was discribed in 2003 by Nabil Seidah, in the Clinical Research Institute of Montreal in Canada. The new protein convertase, the gene for which was located on the short arm of chromosome 1. Meantime, families presenting HeFH had been followed by Catherine Boileau at a famous Parisian hospital , where a mutation on chromosome 1 were identified. Both laboratories worked together and identified the PCSK9 to the condition. Afterwards, diverse experiments from different laboratories demonstrated that high levels of PCSK9 are responsible for LDL receptors stopped function.
Since the late 1980s, statins have been the first-line drugs for lowering cholesterol serum levels but unfortunately, statins doesn’t trigger the expected response in some people and also there are groups of people that can’t take those drugs because of side effects like liver damage, muscle pain or even development of diabetes.
Although PCSK9 inhibitors are an experimental drug, the results of clinical trials are positive, lowering cholesterol levels in patients under the treatment with PCSK9 inhibitors and suggesting clinic benefits as lowering incidence of cardiovascular events.
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| Cholesterol metabolism and PCSK9 inhibitors |