Application Of Follistatin To The Resolution Of Liver Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$330,990.00
Summary
Liver fibrosis or scarring is a consequence of a number of diseases, leading eventually to extensive damage known as cirrhosis. It is a significant health problem both here in Australia and overseas with around 180,000 patients diagnosed each year in the Western world. Cirrhosis arises from many causes, two major groups being patients who contract hepatitis and alcoholics. People with cirrhosis have a much increased risk of liver failure, which requires liver transplantation, or of developing li ....Liver fibrosis or scarring is a consequence of a number of diseases, leading eventually to extensive damage known as cirrhosis. It is a significant health problem both here in Australia and overseas with around 180,000 patients diagnosed each year in the Western world. Cirrhosis arises from many causes, two major groups being patients who contract hepatitis and alcoholics. People with cirrhosis have a much increased risk of liver failure, which requires liver transplantation, or of developing liver cancer, for which current treatments have limited success. We have been studying two proteins, activin and follistatin, both of which are made in the liver. We are interested in activin because it is one of the body's mechanisms to control cell growth, and also seems to stimulate the development of scar tissue. Follistatin is the natural inhibitory substance for activin. It blocks the effects of activin and helps promote cell growth in the liver. We believe that follistatin may also be useful in controlling liver scarring. This process will be studied in animal models of cirrhosis, in the hope that follistatin treatment will reduce the level of liver damage. If successful, this would be important information that would enable us to design treatments applicable to human sufferers of these liver diseases. In another part of the project, we will assess whether activin and follistatin might be useful markers of liver disease. Most patients require a liver biopsy to assess the amount of liver damage, and a simple blood test would be a far easier, less traumatic and cheaper alternative.Read moreRead less
Novel Genes And Protein In Non-alcoholic Fatty Liver Disease: Potential Basis Of A Serum-based Assessment Of Disease Sta
Funder
National Health and Medical Research Council
Funding Amount
$200,000.00
Summary
The most common cause of elevated liver function tests is non-alcoholic fatty liver disease (NAFLD). NALFD is a spectrum of disease ranging from steatosis, to non-alcoholic steatohepatitis (NASH), a condition associated with the development of fibrosis in the majority of individuals. Approximately 20% and 3% of adults are affected with NAFLD and NASH, respectively, and NAFLD is expected to become the next major liver epidemic facing the western world, far exceeding the prevalence of chronic infe ....The most common cause of elevated liver function tests is non-alcoholic fatty liver disease (NAFLD). NALFD is a spectrum of disease ranging from steatosis, to non-alcoholic steatohepatitis (NASH), a condition associated with the development of fibrosis in the majority of individuals. Approximately 20% and 3% of adults are affected with NAFLD and NASH, respectively, and NAFLD is expected to become the next major liver epidemic facing the western world, far exceeding the prevalence of chronic infection with the hepatitis C virus. We obtained liver biopsies from patients with NAFLD, 80% of whom had NASH, and determined the expression profile analysis of each subject using 19,200 element microarrays. Our data demonstrates the concordant differential expression of 130 genes, in subjects with NAFLD that were categorizes into 6 major metabolic and regulatory pathways. Many of these genes represented uncharacterised genes. Utilising an extensive bioinformatics approach we have been able to define the genes and their protein product. The use of these proteins as a diagnostic tool for the detection of NAFLD forms the basis of a provisional patent application. However, measurements of protein levels in tissue and sera from patients with NAFLD are needed for the development of a diagnostic method. Such information would also provide significant insight into the pathogenesis of NAFLD. The AIMS are: 1) Production of antibodies against proteins encoded by candidate genes Expression profile of candidate genes 3) Expression of proteins encoded by candidate genes in patients with NAFLDRead moreRead less
Development Of New Anti-fibrotic Drugs For Prevention Of Diabetic Nephropathy.
Funder
National Health and Medical Research Council
Funding Amount
$133,800.00
Summary
Diabetic kidney disease is the leading cause of kidney failure in the developed world. Currently there is no treatment that reduces the excessive scarring that leads to kidney failure. This project aims to test whether a series of novel compounds that have been specifically designed to reduce scarring can prevent diabetic kidney disease.
Development Of Anti-CXCR7 MAbs For The Treatment Of Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$399,998.00
Summary
Fibrosis is a serious biological process that occurs in many disease conditions, including cancer, inflammation and infections. We have produced antibodies to CXCR7, and these antibodies completely inhibit fibrosis in a mouse model. We plan to develop these antibodies in to a suitable drug for human clinical trials.
Performance And Safety Testing Of The BioQ Cardiac Assist System In A Chronic Ovine Heart Failure Animal Model
Funder
National Health and Medical Research Council
Funding Amount
$142,800.00
Summary
This proposal will test a novel cardiac assist system in safety and performance studies using a chronic sheep heart failure model. This device has been tested in cardiovascular simulators and in an acute animal model showing attractive proof-of-concept data. Specifically, the device increased left coronary artery blood flow and reduced aortic pulse and mean pressures using our novel self-powered fully implantable stand alone device, a potential therapy treatment for heart failure.
Development Of Novel Methods For Non-invasive Measurement Of Cardiac Output And Lung Volume During Anaesthesia
Funder
National Health and Medical Research Council
Funding Amount
$257,970.00
Summary
In Australia approximately 2 million anaesthetic procedures are performed annually. Approximately one patient in 20,000 dies during or shortly after an anaesthetic from complications related to the anaesthetic itself, and as many as one in 170 suffers severe complications. Mortality and severe morbidity are often ultimately associated with lack of oxygen in the tissues. Oxygen is transported from the lungs to the tissues by the blood. The oxygen content of arterial blood is monitored by pulse ox ....In Australia approximately 2 million anaesthetic procedures are performed annually. Approximately one patient in 20,000 dies during or shortly after an anaesthetic from complications related to the anaesthetic itself, and as many as one in 170 suffers severe complications. Mortality and severe morbidity are often ultimately associated with lack of oxygen in the tissues. Oxygen is transported from the lungs to the tissues by the blood. The oxygen content of arterial blood is monitored by pulse oximetry during every anaesthetic, but blood flow is not. Cardiac output is measured in only a very small proportion of anaesthetised patients using intravenous catheters that pass through the heart to the lungs. This procedure is invasive and is associated with significant morbidity and mortality. At present there is no easy way to monitor cardiac output non-invasively during anaesthesia. Our proposed research project, currently underway in conjunction with an industrial partner, is aimed at the development of a reliable, rapidly repeating, non-invasive method for monitoring total cardiac output and lung volume in every patient who has an anaesthetic. The purpose of the new monitor is to ensure that potential problems with oxygen supply to the tissues are detected and corrected promptly. Our new monitoring technique is computer-controlled, can function without intervention by the anaesthetist and has very few side-effects. It can be added to any anaesthetic machine. Such a measurement technique is likely to have an impact on anaesthesia similar to that of pulse oximetry in the 1980's, and, if suitably adapted, is likely to find applications in other fields, such as intensive care, sports medicine, the respiratory function laboratory and in veterinary medicine.Read moreRead less