THE DETECTION AND MANAGEMENT OF DEMENTIA IN GENERAL PRACTICE.
Funder
National Health and Medical Research Council
Funding Amount
$499,977.00
Summary
This research aims to examine a new method and practice guidelines for detection of early dementia. General practitioners will be screened on their ability to diagnose and manage dementia and to distinguish it from other diseases. Patient outcomes - including quality of life, depression, and satisfaction with care and referral indicators - will be examined.
Cognitive Outcome And Therapeutic Interventions For Coronary Artery Disease.
Funder
National Health and Medical Research Council
Funding Amount
$392,104.00
Summary
Dementia is recognized as an increasingly important factor affecting quality of life as people age. Deaths from heart disease are declining, in part due to improved surgical techniques and to the use of less invasive methods to keep arteries open such as coronary stenting. It is now well known that 20 to 60% of patients experience some degree of impairment in thinking ability (cognitive impairment) after cardiac surgery, that this will persist in some of these individuals for years and may incre ....Dementia is recognized as an increasingly important factor affecting quality of life as people age. Deaths from heart disease are declining, in part due to improved surgical techniques and to the use of less invasive methods to keep arteries open such as coronary stenting. It is now well known that 20 to 60% of patients experience some degree of impairment in thinking ability (cognitive impairment) after cardiac surgery, that this will persist in some of these individuals for years and may increase the risk of long-term problems. Cognitive impairment affects people in many ways. While it is not yet known whether the occurrence of cognitive impairment predisposes to dementia, it is thought that Mild Cognitive Impairment (MCI) may do so. We propose to explore the link between MCI and Post Procedural Cognitive Deficit (PPCD) in patients with coronary disease from before the first point of objective diagnosis, i.e. prior to the coronary angiogram, and over a 12-month period, through and subsequent to further treatment interventions such as stenting or cardiac surgery. Our Pilot data suggest that PPCD does indeed occur after angiography, and we propose to identify how long this lasts, whether MCI predisposes to it and whether it is better to wait until it resolves before further interventions are undertaken. In this way we hope to identify the safest treatment strategy for patients with coronary disease that will minimize the occurrence of Cognitive Deficit and possibly longer-term cognitive changes after investigation and treatment for their symptoms.Read moreRead less
A National Resource For Mouse Models Of Mesothelioma
Funder
National Health and Medical Research Council
Funding Amount
$483,643.00
Summary
Mouse models of mesothelioma have led to a greater understanding of the disease and the identification of potential drug therapies some of these have now been translated into clinical trials. In the existing models, mesothelioma cells that have been grown in the laboratory are transplanted into animals by injecting the cells under the skin. Different cell lines with different properties are used in different experimental protocols. This application will fund the establishment of a central resour ....Mouse models of mesothelioma have led to a greater understanding of the disease and the identification of potential drug therapies some of these have now been translated into clinical trials. In the existing models, mesothelioma cells that have been grown in the laboratory are transplanted into animals by injecting the cells under the skin. Different cell lines with different properties are used in different experimental protocols. This application will fund the establishment of a central resource to maintain and distribute these cell lines. In addition, we describe a new transgenic mouse model in which mesotheliomas are rapidly induced in the peritoneal cavity after exposure to asbestos, recreating the natural tumour development much more accurately. These mice have been engineered to express the cancer causing protein of a monkey virus (SV40 large T antigen) in their mesothelial cells because it has been suggested that the virus has a role in the development of mesothelioma. This application also seeks funding to use the MexTAg mice to test the usefulness of different therapies for the prevention or treatment of mesothelioma. These animals give us the ability to investigate the disease in a more realistic environment than previous models. In parallel collaborative studies with other groups investigating different aspects of the biology of this cancer, we plan to analyze the earliest changes in the development of the disease and search for early markers using proteomics and gene expression studies. We anticipate that this model will generate information more directly relevant to understanding the human disease and will provide essential experimental data for clinical trials.Read moreRead less
Transforming Growth Factor Beta Signalling In Malignant Mesothelioma Growth And Collagen Production
Funder
National Health and Medical Research Council
Funding Amount
$509,917.00
Summary
Many cancers contain abundant connective tissue molecules called extracellular matrix (ECM) and data show that interaction of ECM with cells are important in the growth of cancers (1). Changes in expression of ECM and their receptors (integrins) have been associated with malignant changes in cells, enhanced tumour growth and resistance to chemotherapy (2,3). We have recently shown that inhibition of collagen, the most abundant ECM molecule produced by malignant mesothelioma (MM) cells, reduced M ....Many cancers contain abundant connective tissue molecules called extracellular matrix (ECM) and data show that interaction of ECM with cells are important in the growth of cancers (1). Changes in expression of ECM and their receptors (integrins) have been associated with malignant changes in cells, enhanced tumour growth and resistance to chemotherapy (2,3). We have recently shown that inhibition of collagen, the most abundant ECM molecule produced by malignant mesothelioma (MM) cells, reduced MM growth. How cancer cells regulate ECM production and control their growth is unclear but strong evidence suggests the growth factor transforming growth factor-beta (TGFB) plays an important role. We and others showed that MM cells secrete all forms (1-3) of TGFB, and TGFB1,2-like activity has been reported in pleural effusions from MM (4,5). All TGFB forms stimulate MM cells to grow and make ECM (6,7). We showed that high levels of collagen produced by MM are enhanced by TGFB. Small molecules called antisense oligonucleotides (AO) which blocked production of TGFB2 by cells, reduced MM cell growth in soft agar, a characteristic of cancer, and partially blocked MM growth in animal models (4,6). This was supported by studies using soluble TGFB type II receptors, which blocks TGFB1,3 (8), and our studies using TGFB2 specific antibodies, as both studies reduced tumour growth. These findings support a role for TGFB in MM growth. However, all TGFB forms can promote cell grow and collagen synthesis and therefore ways to block all TGFB forms are required to ensure maximal effect. This study will examine the effect of blocking common downstream signalling pathways of all three TGFB isoforms on MM collagen production and tumour growth. These pathways are activated when TGFB binds to its receptors sending messages to the nucleus of the cell to make collagen or grow. By identifying which TGFB signalling pathway is important, we may be able to design novel therapeutic approaches to help treat patients with this disease.Read moreRead less
Gene Based Treatment Strategies For Diabetic Retinopathy
Funder
National Health and Medical Research Council
Funding Amount
$2,630,000.00
Summary
Diabetic retinopathy is the leading cause of blindness in the working population of developed countries and it is an increasing problem in the developing world. Present therapy involves extensive laser destruction of the light-detecting part of he retina. In addition, it is not only effective when administered at an appropriate stage in the disease process. Consequently, there is an urgent need for the development of better, prophylactic, easily administrable and cheaper therapies. This project ....Diabetic retinopathy is the leading cause of blindness in the working population of developed countries and it is an increasing problem in the developing world. Present therapy involves extensive laser destruction of the light-detecting part of he retina. In addition, it is not only effective when administered at an appropriate stage in the disease process. Consequently, there is an urgent need for the development of better, prophylactic, easily administrable and cheaper therapies. This project aims to develop a potentially permanent solution to alleviate diabetes-related blindness in the world. The project combines several very recent scientific advances into one strategy to combat diabetic retinopathy at a molecular level. Vision is our most important sensory organ that cannot be replaced. Thus, human trials can only be conducted following extensive animal safety and efficacy trials. To date the development of new therapies has been seriously hampered by the lack of appropriate, easy to reproduce animal models for different stages of diabetic retinopathy. In addition, it aims to identify new therapeutic agents from molecules that are naturally produced by the retina while fighting the disease. Finally, tested and evaluated in the animal models. The most successful therapeutic candidates will then be further developed for human trials.If successful, our approach will potentially have a major impact on the treatment of diabetic retinopathy and possibly on all diabetic vascular diseases. A single injection might only be necessary to prevent the development of diabetic retinopathy, which would represent a significant weapon in the management of patients. In addition, successful application of secretion gene therapy in the eye might open up the possibility to introduce the same concept for the treatment of larger organs undergoing microvascular changes as a result of diabetes.Read moreRead less
Body Composition Changes In Cardiac Cachexia: Pathophysiology, Quantification And Approaches To Therapy
Funder
National Health and Medical Research Council
Funding Amount
$120,000.00
Summary
Cachexia is weight loss and weakness caused by disease, or as a side effect of illness. Congestive heart failure is a common cardiovascular condition that is accompanied by high mortality (up to 50% over 2 years) and considerable suffering. People with congestive heart failure often develop cachexia. This project will explore the mechanisms responsible for the development of cachexia using an animal model of cardiac cachexia that the researchers have developed. It will be complemented by an exam ....Cachexia is weight loss and weakness caused by disease, or as a side effect of illness. Congestive heart failure is a common cardiovascular condition that is accompanied by high mortality (up to 50% over 2 years) and considerable suffering. People with congestive heart failure often develop cachexia. This project will explore the mechanisms responsible for the development of cachexia using an animal model of cardiac cachexia that the researchers have developed. It will be complemented by an examination of the effects of exercise on measures of cachexia in patients with congestive heart failure. The researchers believe that this study will supply valuable new information about the development of cachexia and lead to new therapies for this syndrome.Read moreRead less
Roles Of Enzymes Of The Dipeptidyl Peptidase Gene Family In Human Liver
Funder
National Health and Medical Research Council
Funding Amount
$79,750.00
Summary
Chronic liver diseases, particularly those caused by autoimmune disease, alcohol and Hepatitis B and C virus infection, are major causes of morbidity and mortality in our community. They are characterised by progressive scarring of the liver which finally leads to liver failure and the need in many cases for organ transplantation. Each year 15,000 Australians become infected, probably for life, with hepatitis C virus. Unless more effective treatments are developed approximately 20% of these infe ....Chronic liver diseases, particularly those caused by autoimmune disease, alcohol and Hepatitis B and C virus infection, are major causes of morbidity and mortality in our community. They are characterised by progressive scarring of the liver which finally leads to liver failure and the need in many cases for organ transplantation. Each year 15,000 Australians become infected, probably for life, with hepatitis C virus. Unless more effective treatments are developed approximately 20% of these infections will progress to liver failure or liver cancer within 30 years. Diabetes afflicts 150 million people, and 90% have Type 2 diabetes. We request funding of our research on a family of enzymes highly prospective as targets for novel therapies for these diseases. We are internationally recognised experts on this enzyme family and on liver disease. The prototype member of this enzyme family, dipeptidyl peptidase (DP) IV, is being targeted by novel drugs that are in phase III clinical trials for Type 2 diabetes. Family member fibroblast activation protein (FAP) is targeted by novel anti-cancer drugs We were first to clone and lodge patent applications for two new enzymes of this family, DP8 and DP9. Our research proposal would lead to determination of whether FAP, DP8 and-or DP9 are valuable targets for novel liver disease therapeutics and facilitate generating the development of such therapeutics by a more thorough understanding of the activities and roles of these enzymes Completion of this project will greatly increase our understanding of these enzymes and their roles in chronic liver injury. This work can potentially lead to the development of specific inhibitors of enzyme function designed to relieve liver damage.Read moreRead less
Enhancing Mental Health In Aboriginal People: Reducing Violence And Developing Resilience
Funder
National Health and Medical Research Council
Funding Amount
$1,771,151.00
Summary
This project aims to determine the best ways to improve the Social Emotional Well Being (SEWB) of the Aboriginal people of Broken Hill, Menindee and Wilcannia. This project will develop a culturally appropriate and evidenced based intervention to break the cycle of ongoing grief, mental illness, alcohol and other drugs and violence. The project will proceed in a number of interrelated phases including extensive community consultations and a baseline survey. The project will then implement and ev ....This project aims to determine the best ways to improve the Social Emotional Well Being (SEWB) of the Aboriginal people of Broken Hill, Menindee and Wilcannia. This project will develop a culturally appropriate and evidenced based intervention to break the cycle of ongoing grief, mental illness, alcohol and other drugs and violence. The project will proceed in a number of interrelated phases including extensive community consultations and a baseline survey. The project will then implement and evaluate an intervention program that provides a community and individual program that adopts evidence-based approaches and modifies them to be acceptable within Aboriginal communities. These interventions aim to break the cycle of violence and mental health problems by teaching adaptive skills to reduce violent behaviours and by providing mental health interventions that reduce disorders that contribute to violence.Read moreRead less
The Pacific OPIC Study - A Four Country Study Of Obesity Prevention In Communities
Funder
National Health and Medical Research Council
Funding Amount
$1,600,580.00
Summary
Obesity is a rapidly escalating, worldwide epidemic. Many countries recognise the need to prevent obesity but there is insufficient evidence about what interventions work. The Pacific Obesity Prevention in Communities (OPIC) Project will provide data on the effectiveness of a range of interventions to prevent obesity among young people in Fiji, Tonga, New Zealand and Australia. Prevention research is particularly required in countries such as Fiji and Tonga because their prevalence of obesity is ....Obesity is a rapidly escalating, worldwide epidemic. Many countries recognise the need to prevent obesity but there is insufficient evidence about what interventions work. The Pacific Obesity Prevention in Communities (OPIC) Project will provide data on the effectiveness of a range of interventions to prevent obesity among young people in Fiji, Tonga, New Zealand and Australia. Prevention research is particularly required in countries such as Fiji and Tonga because their prevalence of obesity is extremely high. The interventions used in this project will be culturally appropriate and include at least 1000 young people in each intervention group. The outcomes of this project will be applicable to both low- and high-income countries. This project will lead to a greater understanding of the socio-cultural, policy, and economic contexts and provide crucial evidence for public health action to prevent obesity.Read moreRead less