Developing a novel pharmacotherapeutic for inflammatory cardiovascular disease

Professor Levon Khachigian, University of New South Wales

2020 Vanguard Grant

Years funded: 2021-2022

Cardiovascular disease kills one Australian every 12 minutes and costs >AUD5B annually. Heart attack and stroke are acute cardiovascular events caused by an arterial blockage preventing blood flow as a result of occlusive atherosclerosis, plaque erosion or plaque rupture followed by thrombosis. Inflammation is an important process in acute coronary syndromes such as unstable angina and heart attack, which can result in sudden death. Inflammation is thought to drive all phases of atherosclerosis, from initiation, progression, and ultimately plaque rupture and infarction, causing further inflammation. Endothelial activation and inflammation are early steps in the development of atherosclerosis and its complications, a process that involves vascular leakiness, white blood cell adhesion and tissue invasion. Several recent large scale clinical trials of antibodies or older repurposed drugs provide strong evidence that cardiovascular disease is a treatable inflammatory disease. Novel small molecule drugs, unlike antibodies, are potentially cheaper to manufacture and have commercial appeal.

This project will:

(a) determine the therapeutic potential of a novel compound, called BT2, which we have identified and characterised from a screen of ~100,000 candidate compounds, in two key experimental models of inflammatory cardiovascular disease;

(b) define the mechanisms by which BT2 protects against cardiovascular disease.

Since BT2 inhibits a wide range of inflammatory factors that drive the development of cardiovascular disease, this novel compound may have broad clinical utility in occlusive vascular disorders and fill much needed gaps in our clinical armamentarium.