A Novel And Unique Protein I-body For The Treatment Of Chronic Kidney Disease Through Targeting CXCR4
Funder
National Health and Medical Research Council
Funding Amount
$768,340.00
Summary
Chronic kidney disease (CKD) is a worldwide public health problem, with adverse outcomes of kidney failure, cardiovascular disease, and premature death. Kidney transplantation and dialysis are the only options for the management of CKD, which results in a significant burden on the health system. The central aim of this project is to develop a novel therapeutic strategy to limit/reverse CKD, which will lead to a researcher-industry partnership in discovery of novel therapeutic agent.
Renal failure is a major cause of morbidity and mortality in persons with diabetes mellitus and accounts for the majority of renal disease worldwide. Renal fibrosis is the end result of progressive kidney disease. The proposed research aims to identify a new strategy by targeting specific channels in kidney cell membranes to arrest the development of enal fibrosis and hence progressive kidney disease caused by diabetes mellitus.
Pathogenic Role Of CDA1 Via Its Profibrotic Action In Diabetic Nephropathy
Funder
National Health and Medical Research Council
Funding Amount
$483,737.00
Summary
We cloned a CDA1 several years ago and found that it played a major role in controlling a series of molecular events leading to production and accumulation of extracellular matrix causing scarring, as seen in diabetic nephropathy. This project aims to study the biological functions and molecular mechanisms of CDA1 in the context of diabetic nephropathy, hence allowing us to consider CDA1 as a molecular target for drug development to treat this condition and related complications.
New Insights Into The Role Of Renal Endothelial Dysfunction In The Pathogenesis Of Glomerular Injury And Renal Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$577,722.00
Summary
This project will ascertain whether abnormal function of endothelial cells contribute to diabetic and non-diabetic kidney diseases, the leading cause of end-stage kidney disease. The outcome of this study will allow us to reevaluate the role of endothelial cells in kidney scarring, lead us to question our current approaches to the treatment and management of chronic kidney disease and eventually may be helpful for the design of novel therapies to treat chronic kidney diseases.
TGF-beta/Smad Signalling In Macrophage-mediated Renal Fibrosis.
Funder
National Health and Medical Research Council
Funding Amount
$683,739.00
Summary
Scarring of organs such as the kidney, lung or liver is a common mechanism leading to organ failure and death. We postulate that a type of white blood cell (the macrophage) can transition into the cell type (the fibroblast) responsible for making the excess collagen that leads to this scarring. If proven, this will be a major advance in our understanding of organ fibrosis and may identify new therapeutic approaches to currently intractable diseases.
Resolvin E1 Is A Novel Anti-inflammatory And Anti-fibrotic Lipid Mediator For The Treatment Of Chronic Kidney Disease.
Funder
National Health and Medical Research Council
Funding Amount
$519,246.00
Summary
This project will ascertain whether a naturally occurring compound, Resolvin E1 with potent anti-inflammatory properties, can effectively halt the progression of experimental kidney disease. We will also test whether Resolvin E1 can exert other potential benefits in suppressing progressive fibrosis of the kidney. The outcome of this study will allow us to evaluate the therapeutical potential of Resolvin E1 for the treatment of acute and chronic kidney diseases.
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
Gamma-Delta Tregs, CD8 Tregs And Selected Natural Tregs To Treat Renal Injury
Funder
National Health and Medical Research Council
Funding Amount
$605,096.00
Summary
Chronic kidney disease (CKD) progresses due to ongoing damage to the kidney. We have identified three types of white cells that can reduce kidney damage in CKD. The first is a unique set of gamma-delta T cells that expand in the kidney and protect against injury. The second is a restricted set of CD8 T cell that can protect against kidney injury. The third are targeted natural regulatory T cells. These studies develop each of these three subsets as potential cellular therapies in CKD.
The Role Of Tissue Hypoxia In The Evolution Of Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$509,391.00
Summary
We will determine how low oxygen levels in the kidney lead to kidney disease. We can now measure the levels of oxygen in kidney tissue in rats 24 hours a day, 7 days a week, in a completely non-invasive way. We will study two common kinds of kidney disease. One, acute kidney injury, can result from administration of contrast agents used in x-ray diagnostic procedures. The other, chronic kidney disease, is common in patients with diabetes or high blood pressure.
New Roles For The Spleen Tyrosine Kinase In Antibody-independent Renal Injury.
Funder
National Health and Medical Research Council
Funding Amount
$574,890.00
Summary
This study investigates the novel hypothesis that a particular cell activation pathway (called Syk) is important not only in antibody-based kidney disease, but that it also plays a previously unrecognised role in other forms of antibody-independent kidney disease. Drugs that inhibit the Syk pathway are in clinical development for treatment of diseases such as arthritis. Hence, a positive outcome of this project could lead to the use of Syk inhibitors in many different types of kidney disease.