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
In Vitro And In Vivo Assessment Of The Funhaler -an Innovative Therapeutic Device For Children
Funder
National Health and Medical Research Council
Funding Amount
$472,750.00
Summary
Aerosol therapy is the most effective form of treatment for children with respiratory diseases such as asthma. While optimising aerosol delivery systems has an important role in increasing the efficacy of asthma therapy, ensuring patient compliance is often the most difficult part of the clinician's role, particularly in the paediatric age group. An innovative small volume spacer device (Funhaler) developed by a West Australian company (InfaMed, Ltd) may help overcome this problem. The Funhaler ....Aerosol therapy is the most effective form of treatment for children with respiratory diseases such as asthma. While optimising aerosol delivery systems has an important role in increasing the efficacy of asthma therapy, ensuring patient compliance is often the most difficult part of the clinician's role, particularly in the paediatric age group. An innovative small volume spacer device (Funhaler) developed by a West Australian company (InfaMed, Ltd) may help overcome this problem. The Funhaler incorporates a spinning toy attached to the outside of the spacer. The toy is activated when the patient breathes through the spacer. The device has been designed to encourage children to co-operate when their asthma therapy is being delivered. The Funhaler is currently in the late development stage. We propose, firstly, to carry out in vitro assessments of drug delivery from the Funhaler compared to the two most widely available small volume spacers: the Aerochamber Plus (Trudell, Canada) and the Breath-A-Tech (Scott-Dibben, Australia). These assessments will be carried out to meet the standards of regulatory bodies worldwide (including the FDA). Secondly, we propose to perform extensive in vivo studie: filter studies to assess drug delivery to the patient; deposition studies to measure drug deposition in the lungs; and a pilot clinical trial to assess the efficacy of the device during medium to long-term use in children aged 2-8 years.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
Steroid-enhancing Selective Casein Kinase Inhibitors: First In Class Novel Inhaled Anti-asthma Agents
Funder
National Health and Medical Research Council
Funding Amount
$538,064.00
Summary
Chronic lung diseases reduce quality and duration of life of 0.5 billion globally (1 in 4 Australians). Current drugs fail to adequately reduce the decline in lung function. This development is based on the discovery of an enzyme pathway contributing to poor lung function. The project will identify the best doses of the drug and the best combinations with existing drugs to reduce the lung scarring and inflammation. These new findings support efforts to secure investment for clinical testing.
Viral Infection And Transforming Growth Factor-beta Impair Glucocorticoid Activity In Epithelial Cells
Funder
National Health and Medical Research Council
Funding Amount
$318,299.00
Summary
Anti-inflammatory types of steroid drugs are commonly used in chronic lung disease including asthma and chronic obstructive pulmonary disease. However, a significant number of sufferers show resistance to the steroid therapy. Our study is developing an understanding of how inflammation limits the anti-inflammatory effects of steroids and we are identifying novel therapeutic targets to improve the effectiveness of treatment of chronic disease.
The Respire_ System: Portable Pulmonary Delivery Platform For Rapid, Flexible And Highly Efficient Treatment Of Elderly, Paediatric And Physically-Compromised Patients With Chronic Respiratory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$599,142.00
Summary
The development of a low-cost miniature drug delivery platform for the treatment of chronic respiratory diseases is proposed. The portable device has already been shown to be significantly more efficient than currently available asthma inhalers. In addition, the device offers the possibility of dose adjustment to account for patient variability, such as age and disease severity, as well as a reduction in patient intervention, thus making it more appropriate for patients unable to self-medicate.
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.
Molecular Characterisation Of TRAIL-regulated Signal Transduction Pathways And Their Role In The Development, Persistence, And Exacerbation Of Allergic Airways Disease
Funder
National Health and Medical Research Council
Funding Amount
$637,035.00
Summary
Molecules that promote the development, persistence, and exacerbation of asthma are only poorly defined. We have discovered a novel signalling pathway that is activated in the airway wall during asthma. Blocking a molecule that activates this pathway ameliorated asthma in mice. We now want to identify all the important components of this pathway and therapeutically modulate them to prevent the development, persistence, and exacerbation of asthma.