Differences Between Physiological And Pathological Cardiac Hypertrophy Offer New Strategies For Treating Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$335,473.00
Summary
The heart becomes large both in athletes as well as in patients with heart disease and failure. In the first instance, the large (hypertrophied) heart has normal or even increased pumping ability (function) whereas in the patient with heart disease the function is depressed and the heart may fail. My studies are directed towards finding out what is the difference in these 2 situations and what mechanisms are responsible for making one big heart pump well and the other big heart pump poorly. Spec ....The heart becomes large both in athletes as well as in patients with heart disease and failure. In the first instance, the large (hypertrophied) heart has normal or even increased pumping ability (function) whereas in the patient with heart disease the function is depressed and the heart may fail. My studies are directed towards finding out what is the difference in these 2 situations and what mechanisms are responsible for making one big heart pump well and the other big heart pump poorly. Specifically my project hopes to identify the genes and proteins responsible for the differences. I have already identified one such gene and I now plan to manipulate this gene by overexpressing it in animals (transgenic mice) with heart failure. I predict that overexpression of this gene will improve heart function in models of heart failure. If the hypothesis is correct, activating genes that are activated in the athlete's heart maybe a potential tool for improving heart function, quality of life and life span in patients with heart failure.Read moreRead less
Electrophysiologic Phenotyping Of Non Ischaemic Cardiomyopathy To Predict Clinical Outcome
Funder
National Health and Medical Research Council
Funding Amount
$374,676.00
Summary
Non-ischemic cardiomyopathy (NICM) is a common cause of heart failure and sudden death. Currently, the guidelines for the management are generalised and do not differentiate patients at high risk of disease progression and sudden death. This project aims to identify the electrical and structural properties of heart, to predict the clinical course in patients with NICM. Identification of high-risk patients will help allocate resources wisely and enable appropriate patient counselling.
Prof Rosenthal proposes to use the Australia Fellowship to create a systems approach to regenerative medicine by bringing today’s breakthroughs in genomics, proteomics, engineering and animal modelling to a critical unanswered biological question: how can we enhance our regenerative capacity in ageing and disease. A successful outcome of this research will pave the way for innovation in clinical treatment of some of the most devastating chronic health problems in Australian society.
Coronary artery disease is the largest single cause of death in Australia, and commonly manifests as heart attack and angina. Congenital heart disease is the most common birth defect. We have identified a gene, Crim1, that is important for heart and coronary artery development. Investigating how this gene functions will lead to a greater understanding of congenital heart disease and may lay the foundation for therapeutics to regenerate damaged hear tissue.
Therapeutic Regulation Of Matrix Metabolism To Stabilise The Biomechanical Properties Of The Sclera In High Myopia
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
Myopia (short-sightedness) is due to the eye being too long. It is a common refractive disorder, affecting some 25-30% of people in developed countries, and results in blurred distance vision. Most myopia is easily correctable with spectacles or contact lenses. However a small, but significant, group of individuals have excessively long eyes and extreme amounts of myopia. These enlarged eyes impose abnormal stresses on the structures inside, particularly affecting the retina which is the light s ....Myopia (short-sightedness) is due to the eye being too long. It is a common refractive disorder, affecting some 25-30% of people in developed countries, and results in blurred distance vision. Most myopia is easily correctable with spectacles or contact lenses. However a small, but significant, group of individuals have excessively long eyes and extreme amounts of myopia. These enlarged eyes impose abnormal stresses on the structures inside, particularly affecting the retina which is the light sensitive part of the eye. Any damage that occurs to the retina in these eyes is, at present, untreatable and irreversible and can result in blindness. In fact, myopia is the 2nd leading cause of blindness amongst adults of working age. In order for the eye to grow so large its white, outer coat (the sclera) must expand without allowing any leaks of the delicate structures and fluids inside. Although the sclera gets very thin as it expands, it has been shown that this process of expansion is not just due to stretching. Before any stretching can occur the biochemical structure of the sclera must change. A complex process, involving the synthesis of structural components and the activity of enzymes that breakdown these structural components, is at work in the sclera of eyes that are rapidly enlarging. The aim of this project is to intervene in the biochemical processes that have already been shown to be involved in excessive eye enlargement. We will use both therapeutic agents and innovative gene therapy techniques to reverse the biochemical changes that occur in the sclera of rapidly enlarging eyes. We predict that these therapies will result in a sclera that is more resistant to being stretched and an eye that has less pathology. The results from this study will provide us with potential therapeutic strategies for the treatment of eyes that are enlarging excessively, thereby giving us the opportunity of preventing blindness in a number of highly myopic individuals.Read moreRead less
The Mechanism Of Action Of Muscarinic Receptor Antagonists In Preventing Axial Myopia
Funder
National Health and Medical Research Council
Funding Amount
$242,545.00
Summary
Myopia (short-sightedness) is the most common refractive error and is due to the eye being too long and, if uncorrected, results in blurred distance vision. Approximately 30% of the population in developed countries, such as Australia, suffer from myopia. In a significant minority of individuals with high degrees of myopia, it is a sight threatening condition and a leading cause of blindness. It has been found that the pharmacological agent, atropine, is effective in preventing myopia in childre ....Myopia (short-sightedness) is the most common refractive error and is due to the eye being too long and, if uncorrected, results in blurred distance vision. Approximately 30% of the population in developed countries, such as Australia, suffer from myopia. In a significant minority of individuals with high degrees of myopia, it is a sight threatening condition and a leading cause of blindness. It has been found that the pharmacological agent, atropine, is effective in preventing myopia in children and in animal models of myopia. However the side effects of blurred vision at near, glare from dilated pupils and the unknown long term effects of chronic atropine treatment have prevented this approach to myopia control from becoming an established treatment in children. It was originally thought that the drug worked by preventing the eye from accommodating for near objects, however it has now been shown that atropine does not to work by this mechanism, but rather by another non-accommodative mechanism. The aim of this project is to determine the mechanism of action of this class of drugs (known as muscarinic antagonists) in preventing myopic eye growth. The project will investigate in which ocular tissues the various subtypes of muscarinic receptors sensitive to these drugs are located and how these are changed in myopic eyes. It will also determine the specific receptor subtype these drugs act on and whether these drugs inhibit eye growth in myopia by altered retinal signalling activity. The results from this study will elucidate the mechanism and route of action of muscarinic antagonists in preventing myopic eye growth. These findings will advance the probability of developing an effective selective muscarinic antagonist drug to use for the prevention of axial myopia without the side effects associated with the broad-band antagonist atropine. The development of such drugs will have a major economic benefit to the Australian population.Read moreRead less
Preparing Australia For Genomic Medicine: A Proposal By The Australian Genomics Health Alliance
Funder
National Health and Medical Research Council
Funding Amount
$25,000,000.00
Summary
The sequencing of the human genome brings the possibility of more accurate identification of the underlying basis of many diseases. This technology has moved so rapidly, however, that clinical access has been limited. In this application, a national alliance of clinicians, researchers, health economists and policymakers will evaluate the case for clinical genomics across inherited disease and cancer, determine how best to deliver this to the patient and train a capable workforce.
Blood Protein Biomarkers For Frontotemporal Lobar Degeneration
Funder
National Health and Medical Research Council
Funding Amount
$184,305.00
Summary
This project will assess blood proteins as biomarkers for different pathogenic forms of frontotemporal dementia (FTD), one of the major neurodegenerative dementias with a very rapid disease progression (mean survival 3 years). At present, it is not possible to predict which pathological variant is present in any given patient. We plan to develop blood protein biomarker assays capable of diagnosing the pathology in vivo.