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New medicines to keep heart failure patients alive

Associate Professor Peter Molenaar, Institution: The University of Queensland

2019 Vanguard Grant

Years funded: 2020-2021


Heart failure is a global health issue with rising prevalence, affecting around 26 million people worldwide, placing significant burden on healthcare infrastructure. In Australia, the prevalence of heart failure is 1.0-2.0% of the population, increasing to over 10% in patients 75 years or older. Despite advances in medications, mortality and readmission rates to hospitals have remained largely unchanged.

The survival rate for heart failure patients is extremely poor, less than 40 % after 5 years. Nearly half of these patients will die suddenly from an abnormal heart rhythm. Therefore, there is an urgent need for new therapies to address the risk of sudden death in these patients. Our overall Aim is:- To develop new medicines to keep heart failure patients alive. We propose to develop a new class of therapeutic agents called 'PDE (Phosphodiesterase enzyme) Activators, designed specifically to prevent sudden death. Our plan is to synthesize new ‘PDE Activator’ molecules that will activate enzymes in the human heart called PDEs.

These enzymes are similar to switches, that can turn off harmful signals that lead to dangerous, life-threatening heart rhythms. ‘PDE Activators’ will be tested in the laboratory directly on human heart. To do this we will obtain hearts from patients with heart failure undergoing heart transplantation at The Prince Charles Hospital, the same patients at risk of sudden death prior to heart transplantation. In our laboratory, we can simulate and mimic the beat of the human heart and the mechanisms that cause sudden death. We will test ‘PDE Activators’ for their ability to prevent the occurrence of dangerous heart rhythms to find the best and most effective ‘PDE Activator’.

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