A new nanodrug to protect the heart from damage after heart attack

2020 Vanguard Grant

Years funded: 2021-2022

Heart disease continues to be the leading cause of death worldwide. Much of the damage caused by heart attacks occurs when the blood supply returns to the heart tissue after a blockage (myocardial ischaemia-reperfusion injury). Treatments that protect the heart from this damage are urgently needed. One of the processes involved in this damage is a change in the shape of the cell’s power house, the mitochondria. Mitochondria can either fuse together or divide into smaller pieces. A protein called Drp1 is needed for mitochondrial division. Treatment with a drug that blocks Drp1, and so reduces mitochondrial division, can protect animals from heart damage. However, until recently, there has not been a specific and potent inhibitor of Drp1 that could be developed into an effective drug for humans.

We have discovered a novel inhibitor of Drp1, called DRPi27. This drug can bind specifically to the Drp1 protein (including human), inhibit mitochondrial division and protect animals from heart damage after heart attack. In this project, we aim to deliver DRPi27 using a new nanoparticle-based delivery system that will target the drug specifically to the injured heart tissue. This will reduce the possibility of unwanted side-effects. We will test the effectiveness of this treatment in a clinically-relevant and established animal model as well as in human heart tissue that we grow in a dish in the lab. These are important steps to test this new drug, before testing in humans.

Our studies will provide a new treatment to improve clinical outcomes in patients after heart attack. The expected outcomes of this new treatment will be to reduce deaths and increase quality of life for patients after heart attack. As well as the clear benefits for patients, this will also reduce direct and indirect healthcare costs for Australia in the long-term.