Identification Of A MicroRNA-based Therapy For The Diabetic Heart
Funder
National Health and Medical Research Council
Funding Amount
$527,723.00
Summary
The incidence of diabetes is rising globally. The heart undergoes adverse remodelling in a setting of type 1 and 2 diabetes (diabetic heart/ diabetic cardiomyopathy) and this is associated with an increased risk for developing heart failure. New therapies for the diabetic heart are greatly needed. In this project we aim to identify and develop a novel therapy for the diabetic heart.
Diabetic Cardiomyopathy: Defining New Mechanisms Of Cardiomyocyte Injury And Loss
Funder
National Health and Medical Research Council
Funding Amount
$609,320.00
Summary
The heart is recognized as an important casualty organ in the progression of diabetes – both type 1 and type 2. We have new evidence that in diabetic and pre-diabetic hearts there is excess breakdown of heart cell structure in order to scavenge metabolic fuel, and that this scavenging can lead to heart cell death. Our goal is to identify ways in which the heart may be protected against this pathology and to identify new molecular targets for treatment of diabetic hearts.
ANNEXIN-A1 MIMETICS: A NOVEL THERAPEUTIC APPROACH FOR TARGETING THE CARDIAC COMPLICATIONS OF DIABETES
Funder
National Health and Medical Research Council
Funding Amount
$815,185.00
Summary
Diabetes affects almost 2 million Australians, creating an increasing heart failure burden. A/Prof Rebecca Ritchie’s team at Baker IDI are interested in the precise role of cardiac inflammation in the progression of cardiomyopathy resulting from diabetes. Using her exciting discovery that a naturally-occurring anti-inflammatory protein is a key regulator of cardiac muscle cell survival and function, A/Prof Ritchie’s team will develop therapies for diabetic cardiomyopathy based on this protein.
Targeting Epigenetic Pathways That Lead To Diabetic Complications
Funder
National Health and Medical Research Council
Funding Amount
$989,948.00
Summary
Glucose remains the major cause of complications in diabetes with prior episodes of high glucose having long lasting effects on blood vessels leading to heart attacks, kidney disease and blindness. We have identified an enzyme Set7 which plays a key role in promoting glucose induced injury. By validating this target using drug and molecular approaches we will strengthen the rationale to develop potent inhibitors of this enzyme in order to reduce the major burden of diabetes, its complications.
Diabetic cardiomyopathy (DiabCM) is common in people with diabetes. It predisposes to heat failure. Its cause remains unclear and there is no specific treatment for DiabCM. Inflammation is a fundamental tissue response to a metabolic insult and it occur in DiabCM. The central hypothesis in this work is that inflammation through myocardial macrophage cells contributes to DiabCM. This hypothesis will be tested in animal models and also in cell culutre studies.
Epigenetic Determinants Of Nephropathy In Adults With Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$532,118.00
Summary
The prevention and successful management of diabetic complications are issues of utmost importance for the health of Australians. We hypothesize that epigenetic pathways partly determine why some individuals with diabetes develop complications of their disease, while others do not, despite a similar duration of diabetes, treatment intensity and mean glucose exposure.
The L-type Calcium Channel As A Reporter Of Successful Morpholino Oligomer Therapy In Treatment Of Duchenne Muscular Dystrophy Cardiomyopathy
Funder
National Health and Medical Research Council
Funding Amount
$595,062.00
Summary
Duchenne Muscular Dystrophy is a fatal muscle wasting disorder. We have previously characterised how the heart fails in a mouse model of muscular dystrophy. We now have preliminary data demonstrating that treatment of mice with morpholino oligomers can rescue cardiac function. This project will fully characterise the effect of the treatment on heart function and optimise therapy regimes with the view to utilising the optimised protocol as a guideline in treating cardiomyopathy in Duchenne Muscul ....Duchenne Muscular Dystrophy is a fatal muscle wasting disorder. We have previously characterised how the heart fails in a mouse model of muscular dystrophy. We now have preliminary data demonstrating that treatment of mice with morpholino oligomers can rescue cardiac function. This project will fully characterise the effect of the treatment on heart function and optimise therapy regimes with the view to utilising the optimised protocol as a guideline in treating cardiomyopathy in Duchenne Muscular Dystrophy boys.Read moreRead less
Cardiomyopathies (heart muscle problems) are the most common inherited heart conditions and represent an important clinical problem. The clinical and psychosocial impact on both the children and their families is significant. The proposed research will improve our understanding of the clinical and genetic basis of childhood cardiomyopathies, and how genetic factors may influence the development, progression, and clinical outcome, including heart failure, transplantation, and sudden death.
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.
How Does Sudden Cardiac Death Occur In Familial Hypertrophic Cardiomyopathy?
Funder
National Health and Medical Research Council
Funding Amount
$1,312,606.00
Summary
Familial hypertrophic cardiomyopathy is a leading cause of sudden cardiac death but the mechanisms for the induction of arrhythmia are unknown. This proposal has the potential to impact sudden death in the young and enable significant expansion of Australia’s research capacity into the treatment of familial hypertrophic heart disease in humans.