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Pathogenesis Of Inflammatory Demyelinating Polyneuropathy
Funder
National Health and Medical Research Council
Funding Amount
$421,980.00
Summary
This project will investigate the cause of Guillain Barre syndrome (GBS), a severe disease that causes paralysis of the limbs, and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), a similar disease that causes either repeated attacks of weakness or chronic weakness. These are important diseases of the peripheral nervous system. In GBS and CIDP, white blood cells move from the bloodstream to phagacytose (eat) the myelin that surrounds peripheral nerve fibres. Removal of myelin interferes ....This project will investigate the cause of Guillain Barre syndrome (GBS), a severe disease that causes paralysis of the limbs, and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), a similar disease that causes either repeated attacks of weakness or chronic weakness. These are important diseases of the peripheral nervous system. In GBS and CIDP, white blood cells move from the bloodstream to phagacytose (eat) the myelin that surrounds peripheral nerve fibres. Removal of myelin interferes with normal function of the nerves. The project will investigate 5 aspects of GBS and CIDP. (1) We will determine which component of myelin is recognised by white blood cells from patients with GBS and CIDP. We have performed preliminary studies indicating that a protein known as PMP-22 and gangliosides may be targets of the immune attack, but this needs to be confirmed. (2) We will study how the immune attack is turned off in GBS. (3) We will study whether and why the immune attack fails to be turned off in CIDP. (4) We will identify genetic markers that may predispose to GBS and CIDP. (5) We will investigate a novel animal model of GBS that we have induced in rats by inoculation with fragments of PMP-22 protein.Read moreRead less
Interrogation Of Two Novel Genetic Susceptibility Loci For Multiple Sclerosis
Funder
National Health and Medical Research Council
Funding Amount
$840,615.00
Summary
This proposal, from the Australia and New Zealand multiple sclerosis (MS) Genetics Consortium, aims to interrogate two new genes that it recently identified as predisposing for the development of MS. Both of the genes underlying these findings are also associated with risk of developing other autoimmune diseases such as type 1 diabetes, rheumatoid arthritis and Graves' disease.
Towards Selective Targeting Of HDACs For Anti-inflammatory Applications
Funder
National Health and Medical Research Council
Funding Amount
$581,892.00
Summary
HDAC inhibitors are anti-cancer drugs that kill rapidly growing cells (like cancer cells). These drugs also have anti-inflammatory properties and so may be beneficial in chronic inflammatory diseases such as as Rheumatoid Arthritis. However, it is unknown how they reduce inflammation. In this project we aim to understand how HDAC inhibitors act as anti-inflammatory agents and to design new HDAC inhibitors with reduced side effects for the treatment of inflammatory diseases.
HTLV-1 is a lifelong infection of immune cells that sustains high infection rates up to 45% in key Australian communities. Despite HTLV-1 causing serious malignancy and inflammatory co-morbidities that shorten lifespan, few biomedical interventions are available. We will examine how the virus grows and alters immune responses to cause disease. With this, we can develop antiviral treatments to reduce virus infected cells, and make new diagnostic biomarker assays suitable for remote settings.
From Bench To Bedside: A New Treatment For Chronic Rhinosinusitis
Funder
National Health and Medical Research Council
Funding Amount
$2,360,520.00
Summary
My research focuses on diseases of the upper airways, in particular chronic relapsing infections and inflammation of the nose and sinus mucosa and on improving wound healing after surgery. My research is translational, aimed at defining new treatments for these diseases. I have invented novel products that improve wound healing after surgery and instruments that help surgeons perform their surgeries in a better and safer way.
There is an unmet need for safe and effective anti-inflammatory drugs. Because P38 MAPK intracellular signalling modulates multiple pro-inflammatory cytokine actions, it appears to be an ideal candidate pathway. P38 inhibitors have been limited by their toxicity within hepatocytes. The aim of this program therefore is to develop agents with enhanced P38 MAPK inhibitory effects as well as reduced liver toxicity based on known structure activity relationships.
Development Of Potent And Selective Blockers Of Acid Sensing Ion Channels For The Treatment Of Pain
Funder
National Health and Medical Research Council
Funding Amount
$578,704.00
Summary
More than three million Australians suffer from chronic pain, and there are few effective drugs available for treating this condition. A 2007 Access Economics Report estimated the economic burden of chronic pain in Australia at $34.3 billion. Acid-sensing ion channels (ASICs) are a recently discovered family of proteins that play a key role in sensing pain. The goal of this project is to develop potent blockers of these channels that can be used to treat patients suffering from persistent pain.
During injury or infection, our body’s immune system protects us by launching inflammation. But uncontrolled inflammation drives common diseases such as cancer, diabetes and Alzheimer’s. This project will reveal how the body deactivates inflammasomes - protein complexes at the heart of inflammation and disease – so we can design better strategies for treating patients with inflammation-driven disease.
Characterisation Of The Anti-inflammatory Properties Of The N-3 Fatty Acid Product, 4-hydroxy-hexenal.
Funder
National Health and Medical Research Council
Funding Amount
$524,559.00
Summary
A concerted effort is being made by experts in the field of omega 3 fats (fish oils) to make specific recommendation on their use to improve human health . We have reasoned that the characterisation of a major oxidation product of these oils could be a key to understanding how these fats benefit us. The project is likely to influence the formulation of fish oils to enhance their health promoting properties.
Impact Of Airway Wall Fibrosis On The Efficacy Of Anti-asthma Drugs
Funder
National Health and Medical Research Council
Funding Amount
$432,750.00
Summary
Most episodes of asthma are controlled or prevented by current medications. In a small, but significant proportion of asthmatics (5-10%) symptoms persist despite the use of the best combinations of anti-asthma drugs. One of the reasons that acute episodes of asthma occur is that the airway tubes slowly change in structure. These changes involve an increase in the amount of collagen (part of the cement between cells) making the airway stiffer. In this project, we are exploring the impact of the s ....Most episodes of asthma are controlled or prevented by current medications. In a small, but significant proportion of asthmatics (5-10%) symptoms persist despite the use of the best combinations of anti-asthma drugs. One of the reasons that acute episodes of asthma occur is that the airway tubes slowly change in structure. These changes involve an increase in the amount of collagen (part of the cement between cells) making the airway stiffer. In this project, we are exploring the impact of the stiffening of the airway on the way that different cells within the airway wall respond to drugs used to treat asthma. Our initial findings suggest that when the airway wall becomes stiffer with more collagen, there is a diminished benefit from the anti-asthma drugs. This new study is designed to identify the molecular mechanisms for the poor response to the anti-asthma drugs. With this knowledge it will be easier to design and test new drugs that are more effective in severe asthma.Read moreRead less