Targeting the inflammatory enzyme heparanase to treat cardiovascular disease

2019 Vanguard Grant

Years funded: 2020-2022

Atherosclerosis is a chronic inflammatory condition resulting in the formation of atherosclerotic lesions or plaques within the walls of arteries, which initially impede blood flow through the artery. Atherosclerotic plaques can eventually rupture to acutely block blood flow through the artery to cause heart attack, which is a leading cause of death in Australia and worldwide. As chronic inflammation is intimately involved at all disease stages there is great interest in identifying the inflammatory mediators involved and developing new anti-inflammatory treatments targeting these pathogenic mediators. Heparanase is a unique pro-inflammatory enzyme that we have recently shown using our novel heparanase gene-deficient mice is a significant inflammatory mediator driving the development of atherosclerosis.

In light of the pro-atherogenic actions of heparanase it is critical to discover and test new classes of heparanase inhibitor drugs as novel therapeutics for treating cardiovascular disease. This project focuses on testing a heparanase inhibitor drug called PG545, which is currently being tested in clinical trials as an anti-cancer drug. The principal aim of this project is to perform pre-clinical testing of the efficacy of heparanase inhibition with PG545 to retard the formation of atherosclerotic lesions and promote the regression and stability of existing advanced atherosclerotic plaques. These pre-clinical studies have the potential to identify a clinically-viable heparanase inhibitor drug as a new therapeutic for treating cardiovascular disease patients in order to reduce their risk of heart attack.