Project Information

• Status: self-initiated project, not funded.

It is proposed that pharmacological inactivation of circulating PCSK9 could effectively reduce blood cholesterol and prevent CVD. The prediction has been convincingly confirmed. Parenteral immunotherapy with anti-PCSK9 monoclonal antibodies in clinical practice can significantly reduce blood LDL-cholesterol in hypercholesterolemic patients and improve their cardiovascular prospects. Recently, selective inhibition of PCSK9 synthesis using small synthetic compounds has been assayed ex vivo. The compounds bind to the PCSK9 nascent polypeptide in the ribosome exit tunnel, stalling its elongation and reducing the production and secretion of the complete/processed protein. We are focusing on both ribosomal stalling of the nascent PCSK9 as well as blocking its interaction with the LDL receptor, which might increase the amount of circulating LDL- cholesterol.