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A Novel Endogenous Inhibitor For The Treatment Of Diabetic Nephropathy
Funder
National Health and Medical Research Council
Funding Amount
$774,606.00
Summary
In various kidney diseases including the most common cause of end stage kidney disease, diabetic nephropathy, identifying the molecular mechanisms responsible for kidney failure are needed to assist in defining new targets and to develop more effective treatments. The proposed studies highlight the potential of a naturally occurring endogenous molecule called Lipoxin, as a modulator of kidney injury which may provide us with a novel approach to tackle the problem of diabetic nephropathy.
We have validated CDA1 as an effective target to retard kidney disease in diabetes using a mouse model where we deleted the CDA1gene. We have also developed a novel agent to inhibit CDA1 in order to retard diabetic kidney disease. In this application, we propose to confirm the efficacy of targeting CDA1 using various diabetes models and a range of strategies to target CDA1. We will also rigorously explore translation of these findings to a new treatment for diabetic renal disease.
To investigate alternative strategies to treat end stage renal disease we have transplanted embryonic kidneys into the wall of the abdominal cavity of adult hosts where they become vascularised and undergo continued but limited development. Strategies to enhance their growth-development and decrease immunogenicity-rejection will now be determined, and the origin of a 'ureter-like' tube of tissue that grows to connect the transplanted embryonic kidney with the recipient bladder investigated.
Lefty - A Novel Anti-fibrotic Molecule For The Treatment Of Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$425,920.00
Summary
Patients with progressive forms of kidney disease go on to develop end-stage renal failure which requires intensive medical support of dialysis or organ transplantation. This is an increasingly common condition in Australia, and the Western world in general. It is devastating for the individual and it places an enormous economic strain upon our healthcare system. In addition, renal failure is a strong and independent risk factor for cardiovascular disease. Current treatments can at best slow the ....Patients with progressive forms of kidney disease go on to develop end-stage renal failure which requires intensive medical support of dialysis or organ transplantation. This is an increasingly common condition in Australia, and the Western world in general. It is devastating for the individual and it places an enormous economic strain upon our healthcare system. In addition, renal failure is a strong and independent risk factor for cardiovascular disease. Current treatments can at best slow the rate of progression of kidney disease, but cannot prevent the relentless progression to end-stage renal failure. Thus, there is a major medical need to be able to halt, and hopefully reverse, this relentless disease. Scarring of the kidney (termed fibrosis) is the common final pathway leading to end-stage renal failure regardless of the nature of the underlying kidney disease. Our preliminary studies have shown that a naturally occurring protein called Lefty can act to inhibit renal fibrosis in cell culture and animal studies. These very promising results have lead to the hypothesis that Lefty can halt, and perhaps even reverse, scarring of the kidney in progressive kidney disease. We will test this hypothesis by using Lefty as a treatment in animal models of renal fibrosis. Further cell culture studies are also planned to examine the mechanisms by which Lefty modulates renal fibrosis. If successful, these studies will provide critical data to support the development of Lefty as a clinical treatment for patients with progressive forms of kidney disease.Read moreRead less
I am a physiologist working to understand how disturbances during pregnancy can alter fetal development and increase the risk of developing adult onset diseases such as cardiovascular disease, renal disease and diabetes. In particular I am interested in how alterations in kidney development may play a crucial role in disease development.
Role Of Vasoactive Hormones And Cytokines In Diabetic Nephropathy
Funder
National Health and Medical Research Council
Funding Amount
$361,650.00
Summary
Kidney disease is a major cause of disability and premature death in the Australian population. In diabetic kidney disease a major factor which accelerates the progression of this disorder is the presence of hypertension. Indeed international and national organisations now recommend aggressive blood pressure treatment in the diabetic patient. This proposal aims to optimise blood pressure treatment in diabetes and evaluate novel more potent blood pressure lowering agents which block within the ki ....Kidney disease is a major cause of disability and premature death in the Australian population. In diabetic kidney disease a major factor which accelerates the progression of this disorder is the presence of hypertension. Indeed international and national organisations now recommend aggressive blood pressure treatment in the diabetic patient. This proposal aims to optimise blood pressure treatment in diabetes and evaluate novel more potent blood pressure lowering agents which block within the kidney important hormonal pathways implicated in diabetic kidney disease. This approach will assist in determining key factors which mediate the damage to the kidney induced by elevated blood pressure. It is anticipated that these studies will lead to more rational, targeted and powerful antihypertensive agents which will retard or prevent the development of diabetic nephropathy.Read moreRead less