Equitable Treatment Of Severe Osteoarthritis In Australia: A Population-based Assessment Of Burden And Barriers.
Funder
National Health and Medical Research Council
Funding Amount
$317,580.00
Summary
Severe hip and knee osteoarthritis is a growing public health problem for Australia, as reflected in the rising demand for joint replacement surgery. However, while severe osteoarthritis is common, how the condition affects a person’s quality of life and ability to maintain their lifestyle is poorly understood. This project will investigate the impact of severe osteoarthritis on the lives of Australians and whether people with the condition have fair and timely access to joint replacement.
Understanding How Endogenous G-CSF Mediates Inflammatory Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$531,485.00
Summary
Rheumatoid Arthritis (RA) is a common chronic inflammatory disease which targets joints. Currently, there is no cure for RA and the available anti-rheumatic drugs have limited efficacy and frequent side effects. Progress has been made in understanding the molecular pathways which drive RA and the disease is characterised by high levels of inflammatory mediators (called cytokines). This finding has led to the development and introduction of specific cytokine inhibitors into clinical practice. The ....Rheumatoid Arthritis (RA) is a common chronic inflammatory disease which targets joints. Currently, there is no cure for RA and the available anti-rheumatic drugs have limited efficacy and frequent side effects. Progress has been made in understanding the molecular pathways which drive RA and the disease is characterised by high levels of inflammatory mediators (called cytokines). This finding has led to the development and introduction of specific cytokine inhibitors into clinical practice. These inhibitors work well for some, but not all, patients. The reason why certain RA patients fail to respond to this treatment is not clear. There is great interest in identifying new cytokines in RA and in developing more effective cytokine inhibitors. Our recent research shows that a cytokine best known for its effect on blood cell development (granulocyte-colony stimulating factor or G-CSF) also plays a major role in experimental models of RA. This discovery has led to two Australian biotechnology companies - Zenyth Therapeutics Ltd., and Murigen Therapeutics Ltd, entering into a partnership to develop G-CSF antagonists for clinical trials. However, before we can take such antagonists to the clinic, we need to conduct careful pre-clinical studies to understand the basis for our findings on G-CSF in much greater detail. This will ensure this new therapy is used in the safest and most effective way.Read moreRead less
Predictors Of The Outcomes For Joint Inflammation And Damage In Recent Onset Rheumatoid Arthritis Patients
Funder
National Health and Medical Research Council
Funding Amount
$255,750.00
Summary
Currently, it is difficult to predict what will happen to an individual patient who presents with newly diagnosed rheumatoid arthritis, either as a result of the natural history of the disease or as a result of drug treatment. It is also difficult to decide which drug treatment to offer a patient and when to decide to change the treatment to obtain a better clinical response. This study will investigate whether it is possible to predict the outcomes for a particular patient with rheumatoid arthr ....Currently, it is difficult to predict what will happen to an individual patient who presents with newly diagnosed rheumatoid arthritis, either as a result of the natural history of the disease or as a result of drug treatment. It is also difficult to decide which drug treatment to offer a patient and when to decide to change the treatment to obtain a better clinical response. This study will investigate whether it is possible to predict the outcomes for a particular patient with rheumatoid arthritis for joint inflammation and joint destruction, based on the findings in the joint lining tissue. This study will also investigate whether it is possible to make decisions on the likely success of drug treatment given to a patient with rheumatoid arthritis based on the initial or subsequent joint lining tissue biopsies. If successful, this study will lead to a greater ability to advise patients about likely outcomes from their condition, either with or without treatment and also to predict whether a treatment is likely to work at an early stage. In addition, this study may identify future potential treatments for rheumatoid arthritis.Read moreRead less
Mechanisms Of Cartilage Destruction And The Effects Of Treatment In Rheumatoid Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$239,830.00
Summary
Rheumatoid arthritis occurs in 1-3% of the population. It is associated with damage to joints causing pain and dificulty with mobility. There are several treatments for rheumatoid arthritis, none of which completely prevents this damage. This study looks at joint tissue and the ways in which damage occurs. It tries to understand why treatment works in some patients and not others. By doing this, the best ways of stopping joint damage will be determined. The study will also tell us the best ways ....Rheumatoid arthritis occurs in 1-3% of the population. It is associated with damage to joints causing pain and dificulty with mobility. There are several treatments for rheumatoid arthritis, none of which completely prevents this damage. This study looks at joint tissue and the ways in which damage occurs. It tries to understand why treatment works in some patients and not others. By doing this, the best ways of stopping joint damage will be determined. The study will also tell us the best ways of looking at whether treatment is working before joint damage occurs.Read moreRead less
Identifying A Novel Aggrecanase In Mouse Cartilage
Funder
National Health and Medical Research Council
Funding Amount
$299,227.00
Summary
Destructive enzymes degrade cartilage in arthritis. Aggrecan is a major structural molecule that gives cartilage its cushioning properties, and aggrecan is also destroyed by harmful enzymes in arthritis. We have discovered a new enzyme that degrades aggrecan. This project aims to identify and study this new enzyme, and to determine its role in aggrecan degradation.
MIF Regulation Of MKP-1 And Glucocorticoid Responses In RA
Funder
National Health and Medical Research Council
Funding Amount
$398,156.00
Summary
Rheumatoid arthritis (RA) is a common chronic inflammatory disease which affects 1% of Australians. Up to 70% of patients are treated with 'steroids', which are drugs with major side effects. Recent research has shown that sensitivity to steroids is controlled by a number of natural proteins, and that balance between these proteins controls the effectiveness of steroids. The proposed research will define the interactions between these proteins.
A type of white blood cell, the macrophage, is a key player in determining the chronicity of inflammatory conditions such as rheumatoid arthritis, atherosclerosis, psoriasis, nephritis, multiple sclerosis etc. Two particular proteins can control macrophage development and functions, both under normal conditions and during inflammation. The project aims to understand this control. More rational ways to suppress inflammation due to aberrant macrophage function should result.
Cartilage Destruction In Arthritis: Mechanism Of Aggrecanase And Matrix Metalloproteinase Action In Vivo And In Vitro
Funder
National Health and Medical Research Council
Funding Amount
$703,180.00
Summary
Arthritis is a disease that causes pain, deformity and disability. The lack of adequate therapies for arthritis is partly a reflection of our limited understanding of the biochemical events involved in disease progression and cartilage destruction. Two distinct families of enzymes are present in cartilage. These are the MMP and the ADAMTS family. These enzyme families are important for cartilage turnover in normal growth and skeletal development. However unregulated enzyme activity resulting in ....Arthritis is a disease that causes pain, deformity and disability. The lack of adequate therapies for arthritis is partly a reflection of our limited understanding of the biochemical events involved in disease progression and cartilage destruction. Two distinct families of enzymes are present in cartilage. These are the MMP and the ADAMTS family. These enzyme families are important for cartilage turnover in normal growth and skeletal development. However unregulated enzyme activity resulting in accelerated cartilage breakdown leads to the pathology recognised as arthritis. While some activities of the MMP and ADAMTS families have been studied in the laboratory, there have been no in vivo studies to determine which family is responsible for cartilage destruction, and which is therefore most appropriate for targeting by drugs. This project will create genetically-modified mice, resistant to either the MMP or the ADAMTS enzymes. The mice will be used in experimental arthritis models to determine which enzymes play the major role in initiating disease, which enzymes are involved in disease progression and which enzymes may be important for repair. In parallel studies, the highly specialised matrix molecule, keratan sulphate, will be studied for its role in cartilage destruction. There is preliminary evidence to suggest that keratan sulphate may be involved in the regulation of ADAMTS activity. The possible direct and indirect modalities of keratan sulphate action will be investigated. The results of this arthritis project will (a) yield new information on the mechanism of disease action; (b) identify targets for the rational design of disease-modifying drugs; (c) elucidate biochemical processes involved in normal skeletal growth and cartilage repair; and (d) provide new in vivo models for testing the efficacy of arthritis therapies.Read moreRead less