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.
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.
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.
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.
Contribution Of Bone Marrow-derived Cells To Renal Fibrosis And Elucidation Of Cell Signalling Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$427,703.00
Summary
This study investigates the contribution of bone marrow-derived adult stem cells to the development of renal scarring, an important process proceeding to end-stage renal disease (ESRD). There is increasing evidence demonstrating that bone marrow (BM)-derived cells can transform into renal cells and participate in the repair of damaged renal blood vessels. Our recent study demonstrated BM-derived stem cells can also transform to renal myofibroblasts, the major cell type that contributes to the de ....This study investigates the contribution of bone marrow-derived adult stem cells to the development of renal scarring, an important process proceeding to end-stage renal disease (ESRD). There is increasing evidence demonstrating that bone marrow (BM)-derived cells can transform into renal cells and participate in the repair of damaged renal blood vessels. Our recent study demonstrated BM-derived stem cells can also transform to renal myofibroblasts, the major cell type that contributes to the development of kidney scarring. This suggests that BM-derived adult stem cells have dual roles: to repair or worsen the development of renal scarring. The present study investigates this adult stem cell's transformation and explores the potential measures to enhance the benefits and to block the harmful roles from these adult stem cells. The importance of BM-derived stem cells in the repair of damaged kidney will be determined and thus will provide preliminary insights into the future utilization of BM-derived stem cells in the treatment of chronic renal disease. Understanding the dual roles of BM-derived stem cells in experimental renal scarring, will lead us to question our current thinking and approaches to the treatment and management of renal fibrosis, and perhaps fibrosis in other organs. Evidence of two opposite roles which BM-derived adult stem cells play in the process of renal scarring may be helpful not only for the design of novel therapies to prevent or retard the progression of renal fibrosis, but also for manipulating adult stem cells for the treatment of renal disease.Read moreRead less
Costimulation In Progressive Non-immune Tubulointerstitial Renal Disease.
Funder
National Health and Medical Research Council
Funding Amount
$434,875.00
Summary
Current treatments for chronic kidney disease are non-specific and frequently ineffective. As a consequence, kidney failure progresses to the stage where patients require dialysis or transplantation to remain alive. Every year about 1700 Australians commence dialysis for this reason and many more die of kidney failure or its complications. This project will examine the role of costimulatory molecules in causing chronic kidney disease (CRD) to progress and their potential as targets for specific ....Current treatments for chronic kidney disease are non-specific and frequently ineffective. As a consequence, kidney failure progresses to the stage where patients require dialysis or transplantation to remain alive. Every year about 1700 Australians commence dialysis for this reason and many more die of kidney failure or its complications. This project will examine the role of costimulatory molecules in causing chronic kidney disease (CRD) to progress and their potential as targets for specific therapy to slow the progression of CRD. In chronic kidney diseases of all types, the kidney becomes infiltrated with inflammatory cells. The amount of inflammation has an important bearing on the severity of kidney failure and the rate at which kidney disease progresses. There are a range of different cells that invade the inflamed kidney, some may worsen disease while some may protect against it. Current treatments are non-selective and may, by suppressing inflammation, prevent both repair and protection. Costimulatory molecules have been shown to be important in the regulation of inflammatory cell activation in transplantation and some autoimmune diseases. We, and others, have evidence to suggest that costimulatory molecules may be pivotal to the development and progression of kidney inflammation in CRD as well. This project will use two robust animal models of human CRD to define the role of costimulatory molecules in progression of kidney disease. If, as our preliminary evidence suggests, costimulatory molecules are shown to alter disease progression, then they will provide excellent targets for new treatments. Eventually, treatment directed against costimulatory molecules may be used as more effective and safer therapy for human kidney disease.Read moreRead less
Apoptosis Signal-regulating Kinase 1 (ASK1) Is A Major Pathway Of Stress-induced Renal Injury In Different Types Of Progressive Kidney Disease.
Funder
National Health and Medical Research Council
Funding Amount
$678,865.00
Summary
Oxidative stress plays an important role in progressive kidney disease. We have identified a stress-activated mechanism (the ASK1 pathway) through which oxidative stress may cause kidney disease. We will perform preclinical studies in models of different types of kidney disease with an ASK1 inhibitor drug and genetically modified mice. These studies will provide new insights into the pathogenesis of kidney disease and will determine the potential of ASK1 as therapeutic target in kidney disease.