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
Opioids As A New Therapy For Inflammatory Arthritis: Immunopharmacological Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$406,527.00
Summary
Arthritis is a chronic inflammatory disorder characterized by joint pain, swelling and stiffness. In fact, 69% of patients present with radiographic erosions and joint space narrowing during the first three years of the disease and it is insufficiently appreciated that patients with rheumatoid arthritis may have a 5-year mortality similar to patients with cardiovascular or neoplastic disease. Prevention of disability and death is the ultimate goal of treatment. However, no cure is yet available. ....Arthritis is a chronic inflammatory disorder characterized by joint pain, swelling and stiffness. In fact, 69% of patients present with radiographic erosions and joint space narrowing during the first three years of the disease and it is insufficiently appreciated that patients with rheumatoid arthritis may have a 5-year mortality similar to patients with cardiovascular or neoplastic disease. Prevention of disability and death is the ultimate goal of treatment. However, no cure is yet available. Instead, current treatment is aimed at relieving symptoms and improving functional performance. There is now a growing recognition that patients with rheumatoid arthritis require more agressive treatment early in the disease, before the development of erosions and deformity. My work has shown for the first time that opioid drugs that act via kappa (k) receptors in the periphery are able to ameliorate the incidence and severity of disease symptoms in rat adjuvant arthritis. Histological and radiological analysis reveals a significant, beneficial effect on joint pathology. The present proposal seeks to build upon this basic information gained in rats into the anti-inflammatory mechanisms of opioid action. I will now apply my expertise to extend this research in animals to human tissues. I am able to combine multiple techniques to carry out a systematic and rigorous study on human synovium from arthritis patients. This work aims to find out why opioids have anti-arthritic actions and might potentially lead to potent, less toxic and less expensive new therapies for arthritis and increase our understanding of the pathogenesis of arthritis.Read moreRead less
Macrophage Migration Inhibitory Factor (MIF) And P53 In Rheumatoid Arthritis .
Funder
National Health and Medical Research Council
Funding Amount
$333,055.00
Summary
Rheumatoid arthritis (RA) is an inflammatory disease affecting approximately 1% of the population. It is characterised by severe inflammation and destruction of joints resulting in significant health problems. The lining tissue of joints is known to be infiltrated by inflammatory cells. In addition to this infiltration of inflammatory cells, there is overgrowth of the normal lining cells of joints. These overgrowing cells contribute significantly to joint damage by invading cartilage and bone an ....Rheumatoid arthritis (RA) is an inflammatory disease affecting approximately 1% of the population. It is characterised by severe inflammation and destruction of joints resulting in significant health problems. The lining tissue of joints is known to be infiltrated by inflammatory cells. In addition to this infiltration of inflammatory cells, there is overgrowth of the normal lining cells of joints. These overgrowing cells contribute significantly to joint damage by invading cartilage and bone and allowing inflammatory cells to reach these areas. The abnormal growth of these cells has been related to the malfunction of certain genes that usually restrain abnormal growth. These genes called tumour suppressor genes are known to be damaged in joint lining cells derived from RA. The best known of these abnormal tumour suppressor genes is called p 53. The product of the p53 gene, the p 53 protein, is particularly important in slowing down the growth of cells. The applicant has recently shown that an inflammatory product called MIF is released in large quantities by joint lining cells in RA. Previous studies by the applicant have shown that blocking MIF using an antibody almost completely prevents arthritis development in a rat model. These studies indicate that MIF is likely to be an important contributor to disease in RA. Recent preliminary studies in the applicant s laboratory have shown that MIF can decrease p53 levels in joint lining cells from RA patients and also that MIF can increase the growth rate of these cells. These preliminary data indicate that MIF may contribute significantly to disease in RA by overriding control of normal cell growth by p53. Confirmation and full exploration of the regulation of p53 expression and function by MIF may highlight a novel way to treat the excessive growth and invasion by joint lining cells which characterises RA.Read moreRead less