Defining The Role Of GILZ In Inflammatory Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$675,030.00
Summary
Corticosteroids are commonly used to treat inflammatory diseases such as arthritis. Their action is based on effects on natural inflammation control pathways. One such pathway is that mediated by the protein known as GILZ (glucocorticoid induced leucine zipper). The function of this protein in disease is not well understood, and the research proposed here will increase understanding of its role. This knowledge could yield new treatments for arthritis and other inflammatory diseases.
A Comparison Of Arthroscopic Synovial Biopsy Based Targeted Biologic Therapy Versus Conventional Therapy In Rheumatoid Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$133,351.00
Summary
This proposed study will investigate if treatment of rheumatoid arthritis (RA) based on biopsy of affected joints’ lining is better than standard therapy (not based on the results of biopsy). Current strategies to treat RA not infrequently result in incomplete disease suppression with potentially resultant joint damage, in part because of lack of definite guidelines to individualise treatment. We propose that therapy on the basis of the analysis of biopsy of joint lining will lead to better dise ....This proposed study will investigate if treatment of rheumatoid arthritis (RA) based on biopsy of affected joints’ lining is better than standard therapy (not based on the results of biopsy). Current strategies to treat RA not infrequently result in incomplete disease suppression with potentially resultant joint damage, in part because of lack of definite guidelines to individualise treatment. We propose that therapy on the basis of the analysis of biopsy of joint lining will lead to better disease control than the currently prevalent approach.Read moreRead less
Glucocorticoids (or 'steroids') are among the most commonly used drugs in the world, chiefly used for inflammatory diseases. However, they have major predictable side effects that have been known for over 60 years. Science has, til now, failed to deliver an alternative that delivers the effects of steroids without the side effects. This application is for funds to support the development of the discovery of the protein known as GILZ towards a treatment to help patients.
Implementation Of A Treat-to-target Remission Strategy For Rheumatoid Arthritis In Australian Public And Private Rheumatology Clinics
Funder
National Health and Medical Research Council
Funding Amount
$178,157.00
Summary
Rheumatoid arthritis (RA) is a common and incurable inflammatory joint disease affecting 2% of Australians. RA is associated with significant pain, disability, loss of work capacity and reduced life expectancy. Research has shown that 'treating to a target' for the goal of remission significantly improves outcomes for people living with RA. This TRIP fellowship will assess the barriers to clinicians and people living with RA managing the disease in a targeted way and develop a package to assist.
Development And Pre-clinical Evaluation Of G-DSF Inhibitors For Inflammatory Joint Disease
Funder
National Health and Medical Research Council
Funding Amount
$88,329.00
Summary
G-CSF was originally identified as a cytokine regulating the production of neutrophils and haemopoietic stem cells from the bone marrow and it is currently used clinically for these properties in bone marrow transplant patients around the world. Anti-cytokine therapy with TNF blockade has recently been introduced for the treatment of rheumatoid arthritis. However, not all patients respond to TNF inhibition. We have gathered extensive data which shows that G-CSF also promotes inflammation in expe ....G-CSF was originally identified as a cytokine regulating the production of neutrophils and haemopoietic stem cells from the bone marrow and it is currently used clinically for these properties in bone marrow transplant patients around the world. Anti-cytokine therapy with TNF blockade has recently been introduced for the treatment of rheumatoid arthritis. However, not all patients respond to TNF inhibition. We have gathered extensive data which shows that G-CSF also promotes inflammation in experimental models of inflammatory joint disease. We propose to develop inhibitors of G-CSF as a novel form of anti-cytokine therapy for inflammatory joint disorders, such as rheumatoid arthritis.Read moreRead less
Understanding The Development Of Autoimmunity In Response To Citrullinated Peptide Antigen Presentation To T Cells In Rheumatoid Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$1,181,793.00
Summary
Rheumatoid arthritis (RA) is a systemic autoimmune disease predominantly affecting synovial joints, in 1% of adults worldwide. HLA-class II genes underlie the major genetic susceptibility to RA. The programme of work brings together 7 investigators from 3 countries to determine how autoimmunity develops to self antigens in individuals at genetic risk of RA and why resistance alleles are protective against RA, in Caucasian, Asian and North American Native populations. We will provide a molecular
Development Of An Anti-GM-CSF Antibody For Treatment Of Rheumatoid Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$283,000.00
Summary
The aim of this project is to develop assays for the evaluation of the efficacy and safety of an anti-GMCSF neutralizing antibody in a Australian first-in-man clinical trial in patients with severe rheumatoid arthritis (RA). This chimeric antibody has been developed by the Ludwig Institute for Cancer Research, Melbourne Branch, in conjunction with KaloBios Pharmaceuticals, Inc., USA. It is intended to use the assays developed in this project to facilitate commercial development of this antibody, ....The aim of this project is to develop assays for the evaluation of the efficacy and safety of an anti-GMCSF neutralizing antibody in a Australian first-in-man clinical trial in patients with severe rheumatoid arthritis (RA). This chimeric antibody has been developed by the Ludwig Institute for Cancer Research, Melbourne Branch, in conjunction with KaloBios Pharmaceuticals, Inc., USA. It is intended to use the assays developed in this project to facilitate commercial development of this antibody, and result in the development of an improved treatment for this devastating disease.Read moreRead less
ADAMTS-5 Activity And The Effect Of A Dominant-negative Mutant
Funder
National Health and Medical Research Council
Funding Amount
$540,235.00
Summary
Cartilage loss is a feature of arthritis and is caused by enzymes. We discovered that loss of a critical cartilage component is caused by the enzyme ADAMTS-5. We also discovered that a mutant form of ADAMTS-5 blocks the normal emzyme, possibly by a novel binding interaction. If we can understand how this interaction works, we can exploit it for the design of new arthritis therapies. This project aims to identify the novel interaction and improve out understanding of cartilage destruction.
The Role Of SOCS-1 And SOCS-3 In Regulating Acute Inflammatory Arthritis.
Funder
National Health and Medical Research Council
Funding Amount
$444,910.00
Summary
Rheumatoid arthritis (RA) is a chronic inflammatory disease which mainly targets joints. The disease causes chronic joint pain, stiffness and loss of joint mobility, leading to increasing difficulty in carrying out day to day activities. Treatment for RA has gradually improved, but remains inadequate for many patients. Although the cause is unknown, progress has been made in understanding the molecular pathways which drive RA. The disease is characterised by the production of high levels of infl ....Rheumatoid arthritis (RA) is a chronic inflammatory disease which mainly targets joints. The disease causes chronic joint pain, stiffness and loss of joint mobility, leading to increasing difficulty in carrying out day to day activities. Treatment for RA has gradually improved, but remains inadequate for many patients. Although the cause is unknown, progress has been made in understanding the molecular pathways which drive RA. The disease is characterised by the production of high levels of inflammatory mediators called cytokines. This finding has led to the development and introduction of specific cytokine inhibitors into clinical practice, although a significant number of patients fail to respond to treatment. An alternative approach to develop new treatments for RA would be to use the body's natural inhibitors to limit the actions of inflammatory cytokines. One such inhibitor is Suppressor of Cytokine Signalling-1 (SOCS-1). Using animal models, we have shown that mice lacking SOCS-1 develop more severe arthritis and have identified the different cell types it acts on. Further studies are still needed before SOCS-1 can be developed as a treatment for RA. We aim to identify the major cell type responsible for the increased severity of disease seen when SOCS-1 is absent. This will allow for treatment to be targetted to the most appropriate cells in the joint. We also aim to study the related molecule SOCS-3, to see whether it has similar effects on inhibiting the severity of disease. These studies will provide more information on the activity of SOCS proteins during inflammatory diseases in general and RA in particular and and may lead to new approaches for the treatment of RA.Read moreRead less