Role Of Amnion Derived Stem Cells In Reducing Lung Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$349,485.00
Summary
Human amniotic epithelial multipotential cells from the term placenta are being studied in a mouse model of pulmonary fibrosis-emphysema to demonstrate their anti-inflammatory, anti-fibrotic, immune-suppresive and lung repair capability. The availability and numbers of these cells from discarded placentas at birth are unlimited and their potential to repair serious lung disease would have strong clinical interest as a new stem cell therapy.
Long-lasting Correction Of The Basic Defect In Cystic Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$458,500.00
Summary
The airway disease caused by the genetic disease cystic fibrosis (CF) is not yet preventable. Current treatments can only limit the gradually-increasing lung disease and is costly. Our new gene therapy technique introduces a correcting gene into affected airway cells, and it has already worked in the first tests in mice bred with CF. Airways in mice are used to test whether the effect is reliable, effective, and lasts long enough to be useful. The gene is introduced into the airway using special ....The airway disease caused by the genetic disease cystic fibrosis (CF) is not yet preventable. Current treatments can only limit the gradually-increasing lung disease and is costly. Our new gene therapy technique introduces a correcting gene into affected airway cells, and it has already worked in the first tests in mice bred with CF. Airways in mice are used to test whether the effect is reliable, effective, and lasts long enough to be useful. The gene is introduced into the airway using special virus delivery-particles, after conditioning the airway to make it receptive to the particles. The method works in normal mice and in CF mice; it gives long lasting gene transfer from a single dose and seems to affect all airway cell types. The gene transfer may also be occurring in airway stem cells, i.e. the mother cells from which grow all the cells of the airway surface. Until now, no-one else has been able to produce prolonged gene transfer in this way, nor arrange gene transfer into stem cells in live airways. There are now a number of things that we must investigate before we could conduct safety and effectiveness trials in larger animals, or consider moving into clinical trials in humans. We need to understand exactly how our conditioning agent works and is it safe; measure how long the gene correction can last actually in our animals; decide if we can we re-dose animals (if needed) without losing effectiveness because of inflammation or immune responses that might occur; and decide how important the airway stem cells are in producing the length of the gene transfer. Because it has been difficult to measure gene correction in CF airways, we will also test new ways we have developed to measure how well the gene correction works in CF airways. The findings of this project will allow us to develop our method to where we can test it in larger animals, to provide a strong, long-lasting gene correction that will be safe for testing in human clinical trials.Read moreRead less
It has recently become apparent that we all make a substance in the lungs called nitric oxide. The amount that we make is increased in diseases such as allergic asthma. This project will study the connection between the allergen being inhaled and the excess nitric oxide being made by cells in the lung. From this research we will have a better understanding of the processess involved and develop better therapies for asthma.
Idiopathic pulmonary fibrosis (IPF) is a fatal disease of unknown cause which is unresponsive to current therapy. This study builds on recent work by this group highlighting the importance of a cell signalling molecule called STAT3 in the development of this disease. In particular, two cell types that utilise STAT3 signalling, epithelial cells and B cells, will be examined to see if blocking their STAT3 responses could be a novel therapeutic approach.
Elucidating The Role Of Mast Cell Tryptases In Chronic Obstructive Pulmonary Disease And Crohn's Disease
Funder
National Health and Medical Research Council
Funding Amount
$620,716.00
Summary
Smoking leads to inflammation that causes emphysema and inflammation in the lung and gut, which are major health problems. Once induced, there is a progressive decline in health and there are no effective treatments. Particular proteins and small genes have been discovered that control inflammation in these diseases. We may be able to control these proteins/genes and stop the progression of emphysema and gut inflammation. This project may lead to a completely new way of preventing and treating t ....Smoking leads to inflammation that causes emphysema and inflammation in the lung and gut, which are major health problems. Once induced, there is a progressive decline in health and there are no effective treatments. Particular proteins and small genes have been discovered that control inflammation in these diseases. We may be able to control these proteins/genes and stop the progression of emphysema and gut inflammation. This project may lead to a completely new way of preventing and treating these diseases.Read moreRead less
Currently in Australia asthma prevalence is high compared with other countries, affecting 10%–12% of adults and 14%–16% of children. This project will determine the contribution of mast cells to the altered function of airway smooth muscle cells and identify how non asthmatic airway smooth muscle inhibits mast cell localisation to it. The findings will provide new targets for asthma therapies and a pathway for prevention strategies, which up until now have been unsuccessful.
Epithelial-Mesenchymal Cell Communication; Towards New Therapeutic Targets For Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$794,596.00
Summary
Fibrosis causes disability and death with millions of people affected each year. Current treatments are limited and there is a need to better understand the changes that drive fibrosis. In this study we will investigate how cells communicate to initiate and drive fibrosis. Using readily available drugs we will test new ways to alter cell communication to stop the disease and thus, develop a common and effective therapy that will change the future for people living with fibrosis.
Immune Recognition Of Upper Airway Microbiota In Early Life As A Determinant Of Respiratory Health In Children
Funder
National Health and Medical Research Council
Funding Amount
$1,135,837.00
Summary
The study will investigate the impact of respiratory infections during infancy on lung & immune function & respiratory health between 3-7 years of age. Children were previously enrolled in a population based birth cohort study (ORChID study) which collected detailed information about the respiratory health during the first 2 years of life with daily respiratory diary & weekly nasal swab collection. In this study lung function & immune function will be assessed annually in the same children (3-7)
Effects Of Allergens On Dendritic Cell Function In Allergic Asthma
Funder
National Health and Medical Research Council
Funding Amount
$254,250.00
Summary
In recent decades, there has been a nearly three-fold increase in the prevalence of allergic diseases such as asthma. Although the reason these diseases have increased in prevalence remains unknown, we suspect the way in which the immune system responds to foreign proteins in the environment may be very important in determining whether an individual develops allergic disease or not. How and why individuals with allergic asthma respond excessively and inappropriately to inhalation of a small rang ....In recent decades, there has been a nearly three-fold increase in the prevalence of allergic diseases such as asthma. Although the reason these diseases have increased in prevalence remains unknown, we suspect the way in which the immune system responds to foreign proteins in the environment may be very important in determining whether an individual develops allergic disease or not. How and why individuals with allergic asthma respond excessively and inappropriately to inhalation of a small range of seemingly innocuous proteins (allergens) is a central question in respiratory medicine and allergy. We propose that investigating the way that antigen presenting dendritic cells (DC) respond directly to allergens will shed important light on this issue, as DC are fundamental to our ability to deal with foreign antigens and to generate an appropriate immune response. The overall hypothesis underpinning this proposal is that allergens induce specific responses in DC from individuals with allergic asthma, and that this contributes to the maintenance and amplification of allergic tissue inflammation in this disease. Understanding the ways in which DC respond to clinically relevant allergens will lead to significant progress in understanding the pathogenesis of allergic asthma. This project was recommended for funding last year, but was relinquished when one of the previous co-investigators on last year's grant was awarded a Program grant.Read moreRead less