Elucidating The Roles And Mechanisms Of Activation Of NLRP3 Inflammasomes And Developing Therapeutic Interventions For Severe Steroid-resistant Asthma
Funder
National Health and Medical Research Council
Funding Amount
$961,929.00
Summary
Severe asthma is a major clinical issue. There are no effective treatments because we don’t understand how it occurs. We have identified a factor called an “inflammasome” that we think causes severe asthma. We have produced a new inhibitor of this factor, and shown experimentally that it may suppress important symptoms of severe asthma. We now aim to work out precisely how this inflammasome causes severe asthma and progress our new inhibitor towards therapeutic development.
Targeting Neutrophil Extracellular Traps To Reduce Inflammation In Severe Asthma
Funder
National Health and Medical Research Council
Funding Amount
$585,240.00
Summary
People with severe asthma, a chronic disease of the lungs, often have many inflammatory cells in the airways called neutrophils. Neutrophils release a meshwork of fibers in a web like trap called NETs, which are made of the cells DNA and other proteins that fight infection. These NETs can promote inflammation in the persons airways. Current asthma treatments have no effect on NETs. This project will measure NETs in the airways and test a new treatment to reduce NETs, and relieve asthma symptoms.
Elucidating The Mechanisms Of Infection-induced, Steroid-resistant Asthma
Funder
National Health and Medical Research Council
Funding Amount
$348,070.00
Summary
Steroid-resistant asthma is an important clinical problem and effective therapies are urgently required. Substantial evidence links bacterial and viral respiratory infections with steroid-resistant asthma, however, how infections are associated with steroid-resistant asthma is not known. This project will investigate the role of specific immune factors, that we have identified, in infection-induced steroid-resistant asthma. Our project may identify new therapeutic targets for this severe form of ....Steroid-resistant asthma is an important clinical problem and effective therapies are urgently required. Substantial evidence links bacterial and viral respiratory infections with steroid-resistant asthma, however, how infections are associated with steroid-resistant asthma is not known. This project will investigate the role of specific immune factors, that we have identified, in infection-induced steroid-resistant asthma. Our project may identify new therapeutic targets for this severe form of asthma.Read moreRead less
Viral Infection And TGFbeta Impair Glucocorticoid Activity In Epithelial Cells
Funder
National Health and Medical Research Council
Funding Amount
$617,699.00
Summary
Chronic inflammatory lung diseases like asthma and smokers lung are treated with combinations of anti-inflammatory drugs. Powerful anti-inflammatory types of steroid drugs are used in more severe disease. Even these powerful drugs are sometimes not effective enough. Our work is developing an understanding of how inflammation limits the anti-inflammatory effects of steroids and we are devising ways to overcome this with new drugs. We aim to improve treatment of chronic inflammatory diseases, espe ....Chronic inflammatory lung diseases like asthma and smokers lung are treated with combinations of anti-inflammatory drugs. Powerful anti-inflammatory types of steroid drugs are used in more severe disease. Even these powerful drugs are sometimes not effective enough. Our work is developing an understanding of how inflammation limits the anti-inflammatory effects of steroids and we are devising ways to overcome this with new drugs. We aim to improve treatment of chronic inflammatory diseases, especially those affecting the lung.Read moreRead less
A New And Effective Approach To Reversal Of Allergic Airways Inflammation By Turning Off Allergic Responses
Funder
National Health and Medical Research Council
Funding Amount
$393,514.00
Summary
Inflammatory diseases like asthma develop from misdirected immune responses. The ultimate goal of therapeutic strategies is to remove or inactivate the cells that cause inflammation while leaving other cells, for example, those required for protection from infectious diseases and tumours, unaffected. Here we propose to test a new way of turning off the inappropriate immune reaction with the goal of preventing or reversing asthma.
This project proposes to identify novel components and develop new inhibitors of an epigenetic pathway known to control the immune cells that cause allergic asthma. Our objective is to use these drugs to treat allergic disease.
Urokinase Is A Key Mediator Of Airway Inflammation And Tissue Remodelling In Asthma
Funder
National Health and Medical Research Council
Funding Amount
$556,425.00
Summary
The scarring of airway tissue in asthma increases the difficulty of breathing. There is no effective treatment for airway scarring in severe asthma. This study looks at how proteins involved in dissolving blood clots influence wound healing and scarring in the airways. A better understanding of airway tissue scarring will lead to possible treatments for more serious forms of asthma which remain a major health and economic burden to our community.
Defining The Roles And Targeting Interferon-epsilon As A New Therapy For Influenza In Asthma And COPD
Funder
National Health and Medical Research Council
Funding Amount
$905,904.00
Summary
Influenza is a major cause of illness and death, especially in people with asthma and emphysema. There are issues with vaccines and current treatments are poorly effective. Effective treatments are urgently required. We have found a new immune factor, interferon-epsilon that is induced and used by influenza viruses to cause infection. We aim to understand how this occurs and to test new treatments for influenza that suppress interferon-epsilon, in healthy and susceptible individuals.
Localised Airway Reactivity As A Determinant Of Asthma Control And AHR
Funder
National Health and Medical Research Council
Funding Amount
$306,562.00
Summary
Asthma morbidity and mortality remain high, with drug cost, days lost from school and work. This may be due to severe asthma in which control cannot be attained. This may be due to localised regions of lung that remain persistently responsive to inhaled irritants. We will examine the location and size of these regions using 3-dimensional ventilation scanning. The potential importance of our findings is in providing a basis for improving treatment in resistant, severe asthma.
Role Of Toll-like Receptor 7 In Rhinovirus-induced Asthma Exacerbation
Funder
National Health and Medical Research Council
Funding Amount
$697,248.00
Summary
One third of the annual asthma-related health care expenditure may be attributable to asthma-related hospitalisations. Even mild asthmatics experience severe exacerbations at a rate of almost one per year1 and those attacks can be fatal. Rhinovirus (RV) causes the majority of asthma exacerbations which may be linked to an impaired antiviral interferon (IFN) response in asthmatics. RV is sensed by Toll-like receptor (TLR) 7, but the role of this innate host defence pathway in regulating antiviral