The Therapeutic Role Of Complement Inhibition In ANCA Associated Glomerulonephritis
Funder
National Health and Medical Research Council
Funding Amount
$600,964.00
Summary
ANCA associated vasculitis is an inflammatory disease involving the kidney filters which is a major cause of chronic kidney failure. Current drugs to treat it are toxic. Less toxic treatments are required. In this study we will explore the potential for new treatments targeting complement (a normal blood protein involved in inflammation) to attenuate this disease in mice. We hope to define the role of complement in this disease and the benefits of inhibiting it before we use it in humans.
New Treatments For Acute Kidney Injury-Targeting The IL-17A Pathway
Funder
National Health and Medical Research Council
Funding Amount
$507,200.00
Summary
Acute kidney injury (AKI) is a common cause of ill-health and death. Despite the frequency and seriousness of AKI no new treatments have developed over the past 40 years. While AKI can occur spontaneously it can also develop after treatment with medications, in particular cancer therapies. In this proposal we will explore the effect of new treatments to prevent AKI. We plan to identify new treatments for patients with AKI, with particular relevance to patients receiving cancer treatments.
Improving The Long-term Outcomes Of The Australian And New Zealand Fontan Population
Funder
National Health and Medical Research Council
Funding Amount
$89,836.00
Summary
The Fontan procedure is the last of a series of operations offered to children born with hearts with a single pumping chamber. Without this procedure these children would die, however, with this procedure their long-term expectations are still uncertain. This study will investigate the long-term outcomes of the Australian and New Zealand Fontan population and how these outcomes can be improved.
Mechanisms Of Infection Triggered Renal Vasculitis
Funder
National Health and Medical Research Council
Funding Amount
$413,900.00
Summary
Kidney disease, including glomerulonephritis, is an important cause of ill-health in Australia. Some forms of kidney inflammation are linked to infection, but we don�t understand why. This project explores products from bacteria, particularly S.aureus, to work out how bacterial infection affects a form of kidney inflammation - ANCA-associated glomerulonephritis. It will establish how infection related signals activate local and immune cells, and define links between infection and the disease.
Inflammation of the kidneys is an important, yet poorly understood cause of kidney disease in Australia. This project will define the role of some of the immune cells, called Th17, that usually act to protect us from infection, but can turn rouge and may cause kidney damage.
Optimising Heart Disease Prevention And Management
Funder
National Health and Medical Research Council
Funding Amount
$4,647,175.00
Summary
As we become older and risk factors such as obesity become more common, our biggest contributor to death and disability, cardiovascular disease (including heart disease), will continue to exert an enormous burden on our health care system and society. We will extend our ground-breaking research on multidisciplinary teams to create new and innovative health care programs to optimise the prevention and management of new heart disease and chronic forms of heart disease.
Improving The Prevention, Treatment And Management Of Cardiovascular & Chronic Disease In The Community
Funder
National Health and Medical Research Council
Funding Amount
$774,540.00
Summary
The identification, prevention and management of cardiovascular and chronic disease risk factors and understanding impact on clinical outcomes is fundamental to improving health and well-being. The program of work encapsulated in this application utilises modern epidemiological research methods involving large scale clinical trials, registries and epidemiological modelling to advance our understanding and provide new directions for cardiovascular disease prevention and management.
Enhancing The Cardioprotective Effect Of Diadenosine Tetraphosphate: Designing Inhibitors Against Ap4A Hydrolase
Funder
National Health and Medical Research Council
Funding Amount
$442,500.00
Summary
Ischemia describes the condition where blood flow in the blood vessels of the heart is decreased or blocked, preventing delivery of oxygen and nutrients to the heart. Ischemic preconditioning is a phenomenon where short bursts of ischemia, followed by reperfusion, actually protect the heart from a subsequent longer period of ischemia. The biochemical signalling events involved in preconditioning are complex and incompletely defined, but most likely involve multiple pathways, although the mitocho ....Ischemia describes the condition where blood flow in the blood vessels of the heart is decreased or blocked, preventing delivery of oxygen and nutrients to the heart. Ischemic preconditioning is a phenomenon where short bursts of ischemia, followed by reperfusion, actually protect the heart from a subsequent longer period of ischemia. The biochemical signalling events involved in preconditioning are complex and incompletely defined, but most likely involve multiple pathways, although the mitochondrial ATP-dependent potassium channel may be in common with most pathways. Pretreatment with the compound diadenosine tetraphosphate (Ap4A) mimics ischemic preconditioning with noticeable reductions in tissue necrosis (cell death). This treatment has been shown in experimental work to protect the heart during periods of stress such as in heart surgery or recovery from an ischemic event. The biological site of action by Ap4A may be the mitochondria ATP-dependent potassium channel or an associated protein. Ap4A can be degraded by enzymes located inside and on the outside of heart cells, notably by two forms of Ap4A hydrolase. We will use antibody assays to understand the specific localization and amount of Ap4A hydrolase before and after ischemia and after ischemic preconditioning in human heart muscle and blood vessels. We propose to determine the structure of the enzyme and use novel computer methods to screen databases for potential inhibitors. These inhibitors of Ap4A hydrolase activity could aid the design of a potent inhibitor that would prevent Ap4A hydrolase from degrading Ap4A and therefore enhance the cardioprotective properties of Ap4A as well as minimizing side effects from the break down of Ap4A. We will also use these inhibitors and other known non-degradable Ap4A analogues in bioassays to test the relative significance of Ap4A hydrolase present in different cellular locations.Read moreRead less
Rapidly giving intravenous fluid to prevent or treat shock (fluid resuscitation) is one of the commonest treatments given to critically ill patients. Current guidelines recommend crystalloid solutions but it is unknown whether any particular crystalloid is better than others. This trial will determine whether the use of one of two crystalloid fluids, saline or PlasmaLyte, reduces the risk of organ injuries, such as kidney failure, and improves patients chances of surviving critically illness.
Prevention And Treatment Of Chronic Heart And Kidney Disease Via Epidemiological, Pharmacol Device And Cell-Based Approaches
Funder
National Health and Medical Research Council
Funding Amount
$5,795,334.00
Summary
Heart failure describes where the heart cannot pump adequately to meet the needs of the body. This condition has a high mortality despite recent advances in therapy, therefore, there is an urgent need for new approaches to this condition. The present grant aims to: (1) identify patients at high-risk for future development of this condition where early intervention with drugs may reduce or prevent the development of new heart failure; (2) use novel drugs, devices and stem cell therapies to identi ....Heart failure describes where the heart cannot pump adequately to meet the needs of the body. This condition has a high mortality despite recent advances in therapy, therefore, there is an urgent need for new approaches to this condition. The present grant aims to: (1) identify patients at high-risk for future development of this condition where early intervention with drugs may reduce or prevent the development of new heart failure; (2) use novel drugs, devices and stem cell therapies to identify ways to better treat patients with existing disease; (3) focus on the effect of heart failure on the kidney and vice versa via early diagnosis and treatment strategiesRead moreRead less