Pre-clinical Development Of A Novel Anti-fibrotic, Anti-inflammatory Compound To Treat Diabetic Heart Disease
Funder
National Health and Medical Research Council
Funding Amount
$488,391.00
Summary
Diabetic patients are prone to developing chronic heart failure. In the diabetic heart, scar tissue accumulates within the muscle (fibrosis), impairing function. We have developed a new drug to treat fibrosis in diabetic kidney disease (FT-11), and have approval for pre-clinical development of this drug. We now aim to test whether FT-11 is also effective in reducing fibrosis in the diabetic heart, and whether this can prevent heart failure in an animal model of diabetic heart disease.
The adult heart has an extremely limited capacity for regeneration. In contrast, I recently discovered that the newborn heart can completely regenerate following a heart attack. How and why the heart loses this regenerative capacity after birth is not known. This Fellowship aims to unravel the genetic circuits that govern cardiac regenerative capacity. The proposed research program will develop novel therapies for heart regeneration through molecular targeting of regulatory RNA molecules.
Modulation Of TGF-beta Signaling By CDA1 In The Diabetic Vasculature
Funder
National Health and Medical Research Council
Funding Amount
$524,004.00
Summary
Cell Division Autoantigen 1 (CDA1) is a molecule we identified several years ago. Recently we found that CDA1 played an unique role in causing blood vessels to scar and become stiff by hijacking and controlling the existing transforming growth factor-beta (TGF-beta) signaling pathway. We will explore the possibility to use this unique property of CDA1 to treat the blood vessel hardening and related diseases such as atherosclerosis and heart attacks, particularly in the setting of diabetes.
Cardiac Fibrosis In Hypertensive Heart Disease: Cellular And Molecular Mechanism
Funder
National Health and Medical Research Council
Funding Amount
$631,979.00
Summary
Cardiac fibrosis due to excess collagen accumulation in the heart is a major cause of heart failure associated with high blood pressure and greatly increases the risk of sudden death. At present there are no effective therapies to prevent cardiac fibrosis. Understanding how fibrosis develops and identifying the cells and factors responsible will lead to development of novel therapies for cardiac fibrosis.
Preclinical Relaxin Therapy To Reverse Cardiac Fibrosis And Gain Functional Benefits
Funder
National Health and Medical Research Council
Funding Amount
$724,754.00
Summary
Cardiac fibrosis is a key factor promoting heart disease and onset of complications including arrhythmias and heart failure. There is urgent and unmet need of drugs that can reverse fibrosis. By documenting anti-fibrotic action of a peptide hormone relaxin, CIA and his team will test therapeutic effect of relaxin in heart disease models focusing on fibrosis-reversal and functional gain, particularly arrhythmias. This work would promote development of relaxin as a new cardiovascular drug.
This fellowship support will allow A/Prof Xiao-Jun DU to pursue his recent pre-clinical research findings on novel therapeutic interventions for cardiovascular diseases. He will particularly focus on new treatment of accumulation of excessive scar tissues (fibrosis) in the heart and large arteries following disease and cardiac inflammation, factors knowing to play pivotal roles in progression of cardiovascular diseases.
Ventricular Remodelling In Cardiomyopathy _ Impact On Ventricular Physiology And Cardiovascular Outcome.
Funder
National Health and Medical Research Council
Funding Amount
$123,337.00
Summary
Diffuse myocardial fibrosis is the widespread deposition of scar tissue in heart muscle and is a common final pathway of cardiac disease. A new technique (contrast-enhanced T1 mapping) using cardiac magnetic resonance imaging can non-invasively detect this scarring. The proposed research intends to further determine the significance of diffuse myocardial fibrosis in cardiac disease, evaluate its link with diastolic heart failure and examine the potential therapeutic role of anti-fibrotic agents.
Fibrosis is a common feature of many forms of heart disease. Despite the recognised central role of reactive oxygen species (ROS) in cardiac fibrosis, antioxidant approaches have failed in clinical trials. We have discovered a new mechanism for ROS-mediated fibrosis that is depleted in human heart failure, and will test an innovative therapeutic approach that is imminently translatable given the development by members of our team of a specific peptide blocker effective in blocking this pathway.