Many approaches to the prevention and treatment of allergy and associated asthma are dependent on the identification of the allergens producing the inflammation. This applies to new methods of determining the exposure to allergens and measuring the effectiveness of procedures which minimise allergen exposure. Diagnostic and immunotherapeutic measures require reliable preparations of allergens. The presence of important allergens in extracts however can be variable and often low so it important t ....Many approaches to the prevention and treatment of allergy and associated asthma are dependent on the identification of the allergens producing the inflammation. This applies to new methods of determining the exposure to allergens and measuring the effectiveness of procedures which minimise allergen exposure. Diagnostic and immunotherapeutic measures require reliable preparations of allergens. The presence of important allergens in extracts however can be variable and often low so it important that the allergens be identified and monitored. It is also important that new forms of immunotherapy being developed consider the responses to all allergens. Allergy to the cat is, behind house dust mite, the second most frequent allergy associated with asthma in most developed countries and brief exposure to a cat frequently induces life-threatening attacks. Almost all of the study of cat allergens have concentrated on a single allergen called Fel d 1. Although it importance is undisputed critical reading of the literature show it is only responsible for 50% of the IgE binding in cat extracts and recent work on cross allergy to cat and dogs and experimental therapy based on Fel d 1 point to the importance of other allergens. Experience with other source of allergens has shown that at least several allergens are usually important. It is also apparent from other studies that some allergens which are difficult to detect in extracts, and cannot be readily studied by immunochemistry are important. This project will use both cDNA cloning and immunochemistry to identify and characterize the other cat allergens and determine there relative importance. In particular it intended that they can be used, along with Fel d 1, to develop new types of immunotherapy.Read moreRead less
Investigating The Impact Of Ethnicity On Asthma: Determining Risk Factors, Modifiers, Clinical Phenotypes, And Differential Response To Treatment.
Funder
National Health and Medical Research Council
Funding Amount
$125,396.00
Summary
Asthma is a common disease in Australia with significant burden on both patients and the public healthcare system. Patients from ethnic minorities have disproportionately worse outcomes and current treatment guidelines are based on research among Caucasian-based populations. My PhD will describe differences in clinical characteristics, outcomes and response to treatment between ethnic groups. The overall aim of my PhD is to develop highly effective asthma treatment for ethnic minorities.
Mimotopes For The Investigation And Therapy Of Allergic Disease
Funder
National Health and Medical Research Council
Funding Amount
$203,296.00
Summary
10% of children now use regular asthma medication. The current treatments dampen allergic inflammation but 25% of asthmatic children, all under high medication, need multiple visits to the doctor, emergency treatment or hospitalisation,. Immunotherapy has, since 1911, used repeated injections of allergens. The end result has often been successful and lasting but the response has been unpredictable and requires years of multi-injection treatment. The challenge is to develop effective, applicable ....10% of children now use regular asthma medication. The current treatments dampen allergic inflammation but 25% of asthmatic children, all under high medication, need multiple visits to the doctor, emergency treatment or hospitalisation,. Immunotherapy has, since 1911, used repeated injections of allergens. The end result has often been successful and lasting but the response has been unpredictable and requires years of multi-injection treatment. The challenge is to develop effective, applicable immunotherapy which, like vaccines use few injections. Mimotopes provide a new opportunity. Studying the parts of the allergens recognized by the immune system (epitopes) can reveal important phenomena undetectable with whole allergens; and single epitopes may be a powerful avenue to effective immunotherapy. The therapy can be targeted to a selected arm of the immune system for maximal effect and the immediate side effects induced by cross linking antibodies with two epitopes can be avoided. Allergens interact with two types of lymphocyte, the T and B cells. T-cell epitopes can be easily studied because they comprise short regions of proteins which can be synthesized. B-cell (and antibody) epitopes are shapes formed by the interaction of several parts of a protein which cannot be represented by a simple sequence. The mimotope technology uses random peptides to obtain a shape which mimics the B-cell epitope. Here mimotopes will be produced and used to study the common specificities recognized in allergic responses to house dust mite allergens to develop new types of therapy. Importantly recent information shows that B-cell epitopes can be used to modify both T and B-cell function.Read moreRead less
Waxing And Waning Of Asthma During Transition From The Teens To Adulthood: Identification Of Immunophenotypic Markers To Predict Disease Trajectory And Guide Development Of Treatment Strategies To Prevent Progression To Chronicity
Funder
National Health and Medical Research Council
Funding Amount
$736,166.00
Summary
The project will seek to identify biomarkers in teenage/young adult asthmatics that can distinguish between those who are "growing out" of the disease, versus those who are progressing towards chronic severe asthma. This knowledge will inform the development of more effective treatment programs for this age group.
Multi-centre, Multi-disciplinary Study Using A Systems Biology Approach To Investigate Immunomodulation In Children With Acute Wheeze
Funder
National Health and Medical Research Council
Funding Amount
$1,895,107.00
Summary
The concept that immunomodulation using naturally-occurring bacterial agents can treat asthma has reached international prominence. This is backed by strong epidemiologic and clinical trial data. However, detailed knowledge of the immunological mechanisms involved is essential to allow more focused therapeutic agents to be developed. The proposed multi-disciplinary immunomodulation study in 200 children aims to provide this essential information using an advanced systems biology approach.
Evaluation Of A Financial Incentive To Improve The Use Of Preventive Medicines By People With Asthma
Funder
National Health and Medical Research Council
Funding Amount
$137,860.00
Summary
Rising costs are threatening the future viability of the Pharmaceutical Benefits Scheme. New approaches are needed to address this challenge, including developing financial incentives for consumers to use effective low cost medicines in preference to higher cost alternatives. This study will develop a consumer incentive for use of low cost asthma preventer medicines, model the economic effects of this and bring together stakeholders to examine the policy and practice changes needed to implement ....Rising costs are threatening the future viability of the Pharmaceutical Benefits Scheme. New approaches are needed to address this challenge, including developing financial incentives for consumers to use effective low cost medicines in preference to higher cost alternatives. This study will develop a consumer incentive for use of low cost asthma preventer medicines, model the economic effects of this and bring together stakeholders to examine the policy and practice changes needed to implement the incentive.Read moreRead less
Asthma Prevention And Treatment Using UVB Radiation-induced Immunomodulation
Funder
National Health and Medical Research Council
Funding Amount
$496,446.00
Summary
The prevalence of asthma is increasing despite the adoption of modern expensive drugs. Our studies suggest that exposure of skin to an erythemal dose of the wavelengths of UVB radiation found in sunlight can suppress responses to allergens encountered in the airways. We are requesting support to study the mechanisms in mice by which exposure to UVB radiation on their shaved backs can reduce inflammation in the airway mucosa upon allergen exposure. Whole body immunomodulatory effects of UVB radia ....The prevalence of asthma is increasing despite the adoption of modern expensive drugs. Our studies suggest that exposure of skin to an erythemal dose of the wavelengths of UVB radiation found in sunlight can suppress responses to allergens encountered in the airways. We are requesting support to study the mechanisms in mice by which exposure to UVB radiation on their shaved backs can reduce inflammation in the airway mucosa upon allergen exposure. Whole body immunomodulatory effects of UVB radiation have been previously described but have not been scientifically linked with asthma development. This is a very new and novel research area which supports century-old anecdotal reports that holidays at beach and mountain resorts associated with increased UVB exposure are beneficial in asthma treatment. This is a proof of principle study. If we can confirm that UVB is immunomodulatory and better understand the mechanisms by which UVB suppresses inflammation in the airways, we will investigate the potential of non-carcinogenic, UVB-induced, skin-derived intermediary molecules to have the same regulatory effects.Read moreRead less
Inhibition Of Allergic Airway Inflammation By Nanoparticles
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
Inhaled air pollution particulate matter causes asthma exacerbations, with 'ultrafine' nanoparticles thought to play a major role. Unexpectedly, we recently found that, by contrast, administration of inert ultrafine nanoparticles prevents allergic airway inflammation. We will identify the key particle physical and chemical properties associated with this novel type of disease inhibition, study particle effects in clinically-relevant disease models and identify mechanisms of action.