Dr Ashish Misra, leader of the Atherosclerosis and Vascular Remodelling Unit at HRI, has been awarded the Perpetual IMPACT grant.
Dr Misra’s research focuses on understanding how the drug colchicine protects against atherosclerosis.
Atherosclerosis is a progressive disease where fatty plaque builds up in the arteries. It is the primary cause of cardiovascular disease – the leading cause of death worldwide.
By the age of 20, most people in Australia will have some degree of atherosclerosis.
“This exciting research will bring together leaders in cardiovascular genetics, atherosclerosis and cardiology from across Sydney and New York to investigate how colchicine acts to reverse atherosclerosis,” says Dr Misra.
A 2019 Canadian clinical trial showed that colchicine reduced the risk of cardiovascular events by 34 per cent, but beyond reducing fatty build ups, its exact mechanism is unclear. Understanding this mechanism could uncover new pathways for future treatment approaches and potentially lead to widespread clinical use.
Previously, Dr Misra made a groundbreaking discovery in 2018 that changed our understanding of the way atherosclerosis progresses. Until then, it was believed that smooth muscle cells (SMCs), found in the blood vessel wall, remained stationary while atherosclerotic plaque formed over them. Dr Misra revealed that certain SMCs migrate into the plaque and differentiate into cells called macrophages, which make plaque unstable.
Dr Misra hypothesises that colchicine promotes the regression of atherosclerosis because it causes the migratory cells to turn back into regular SMCs and therefore stabilises the plaque. This will be tested in his research project.
“Success in this project will represent a paradigm shift as it will establish the first-ever therapy for atherosclerosis that works by changing the biochemical properties of cells,” Dr Misra says.
“Colchicine is an inexpensive drug, and if we can prove its effectiveness in treating atherosclerosis, it could become an easily accessible and widely used treatment to reduce cardiovascular disease in Australia, including amongst those at highest risk, such as remote Indigenous communities.”
Dr Misra also collaborates with Associate Professor Sanjay Patel, leader of the Coronary Diseases Group at HRI. Assoc Prof Patel has demonstrated that colchicine is successful in reducing atherosclerosis and heart attacks, in work that is now showing promising outcomes in clinical trials.
The Perpetual IMPACT grant is funded by the Walter and Eileen Ralston Trust. Since 2016, both the Walter and Eileen Ralston Trust and Ramaciotti Foundations (both managed by Perpetual) have made significant contributions to HRI’s research into colchicine as a treatment for cardiovascular disease.