Improved Gene Therapy Strategies For Primary Pulmonary Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$370,517.00
Summary
Many people develop problems with the blood vessels in the lungs, which then leads to a narrowing of these vessels and consequently a back-pressure strain on the heart. These disorders can arise from inherited diseases of the blood vessels themselves, or from accquired lung disease (for example due to smoking or chronic infections). At present there are few treatments which have any benefits for these patients and many must undergo lung or heart-lung transplantation. This project is desigened bo ....Many people develop problems with the blood vessels in the lungs, which then leads to a narrowing of these vessels and consequently a back-pressure strain on the heart. These disorders can arise from inherited diseases of the blood vessels themselves, or from accquired lung disease (for example due to smoking or chronic infections). At present there are few treatments which have any benefits for these patients and many must undergo lung or heart-lung transplantation. This project is desigened both to find out new information about the disease process that affects the lung blood vessels and to offer a strategy for new treatments. The project will use a crippled form of the cold virus to deliver genes to the lining of the lung blood vessels, then see what impact that has on the pressure within the vessels and the ways in which they respond to certain stresses. These studies will be carried out using laboratory animals. If successful, it may be possible to eventually design such viruses to deliver genes which have a helpful therapeutic impact on the disease in patients.Read moreRead less
Breathing In Chronic Heart Failure: Is There Novel Pulmonary Compensation?
Funder
National Health and Medical Research Council
Funding Amount
$312,021.00
Summary
Chronic heart failure (CHF) is a growing modern epidemic and therefore a costly health burden in Australia. Not only is it associated with a high mortality rate, symptoms of CHF are a major cause of patient suffering. Shortness of breath and exercise intolerance are both indicators of a link between CHF and lung function. There are a number of different ways in which CHF may be impacting on breathing and in this project we will be utilising an animal model to examine some of them. Firstly, the l ....Chronic heart failure (CHF) is a growing modern epidemic and therefore a costly health burden in Australia. Not only is it associated with a high mortality rate, symptoms of CHF are a major cause of patient suffering. Shortness of breath and exercise intolerance are both indicators of a link between CHF and lung function. There are a number of different ways in which CHF may be impacting on breathing and in this project we will be utilising an animal model to examine some of them. Firstly, the lung secretes a substance called surfactant which assists in normal breathing by decreasing surface tension in the lung. Previous studies in our laboratory have suggested an increase in surfactant production during CHF. In this project we will further examine this process to see if increased surfactant can aid breathing by decreasing surface tension during CHF. Secondly, we will examine the contribution made by the chest wall, increased heart size, lung volume and blood pressure during CHF on breathing. Thirdly, one of the problems thought to inhibit breathing in CHF patients is an increase in fluid in the lungs. The final stage of this project will examine the trasport of fluid into and out of the lung during CHF. This project will not only increase our understanding of the processes affecting breathing in response to CHF, but will also provide information for the development of potential therapeutic targets.Read moreRead less
Cytokine And Macrophage Determinants Of Pulmonary Inflammation During Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$455,899.00
Summary
Tuberculosis (TB) infects 33% of the world, causing over 2 million deaths per year. TB disease causes damaging lung pathology and new therapies to treat the infection and moderate inflammation are urgently required. TNF is essential for immunity to TB, acting to modulate inflammation. This grant will determine how soluble and membrane- bound TNF regulate the cellular and cytokine control of TB pathology and may lead to new therapies to limit inflammation in TB and other inflammatory diseases.
Peroxisome Proliferator Activated Receptor Gamma Is A Novel Therapeutic Target For Inflammation And Remodelling In Asthma
Funder
National Health and Medical Research Council
Funding Amount
$307,436.00
Summary
Asthma affects over 2 million Australians with 300 deaths each year. Current drugs are not always effective. A new approach is to reduce the thickening and stiffening of the airway muscle found in asthma. Rosiglitazone, an antidiabetic drug in current use, inhibits growth of airway muscle in the test tube and chest tightening in a mouse model of asthma. Cells from asthmatics will be used to confirm these positive findings, and to support rapid clinical evaluation of this drug to benefit patients ....Asthma affects over 2 million Australians with 300 deaths each year. Current drugs are not always effective. A new approach is to reduce the thickening and stiffening of the airway muscle found in asthma. Rosiglitazone, an antidiabetic drug in current use, inhibits growth of airway muscle in the test tube and chest tightening in a mouse model of asthma. Cells from asthmatics will be used to confirm these positive findings, and to support rapid clinical evaluation of this drug to benefit patients.Read moreRead less
Genetic Dissection Of The Function Of The Src Family Tyrosine Kinase Hck In Inflammatory Lung Disease
Funder
National Health and Medical Research Council
Funding Amount
$323,750.00
Summary
This project aims to identify better and safer treatments for serious, life-threatening inflammatory lung diseases, such as Chronic Obstructive Lung Disease (COPD), which affect over 600 million people worldwide and are a major health problem in Australia. There are no effective treatments that can reverse or slow these diseases. The research is based on our recent discovery that an enzyme called Hck might play a very important role in lung disease. We used mice in which a genetic method had bee ....This project aims to identify better and safer treatments for serious, life-threatening inflammatory lung diseases, such as Chronic Obstructive Lung Disease (COPD), which affect over 600 million people worldwide and are a major health problem in Australia. There are no effective treatments that can reverse or slow these diseases. The research is based on our recent discovery that an enzyme called Hck might play a very important role in lung disease. We used mice in which a genetic method had been used to change Hck into its active form. The mice appeared normal when they were born but developed a progressive lung inflammation that resembled serious human lung diseases. Surprisingly, the mice also displayed enhanced responses to substances from bacteria that can infect the lung - a so-called innate immune response. This led us to conclude that the main problem in the mice was actually enhanced innate immunity - which is usually protective - turning against the lung to cause disease. To understand exactly what controls this fine balance between protection and lung damage, we will use new and sophisticated gene modification methods that allow us to target changes in Hck activity to specific cells that we suspect are the main cause of the disease. In doing so we will add special tags into these cells, so that we can isolate the controlling molecules in the disease process. We are particularly interested in a cell called the macrophage, a major defensive cell in the lung that is also known to be capable of causing lung disease. Our aim is to find disease-controlling molecules that could be blocked with new drugs that would suppress disease but spare defenses against lung infections.Read moreRead less