Rheumatoid arthritis (RA) is an auto-immune disease and characterized by chronic inflammation in the joints that results in the destruction of cartilage and underlying bone.
The cartilage and bone destruction that occurs in rheumatoid arthritis (RA) results from its invasion by inflammatory tissue (pannus) which grows from the synovium (joint lining). The presence of degrading enzymes (proteases) and new blood vessels (angiogenesis) plays an important role in joint destruction. However, the factors which control protease activity or angiogenesis are poorly understood.
Our research will determine whether activated protein C (APC) reduces the severity of rheumatoid arthritis (RA) by preventing the abnormal immune response and subsequent inflammatory response. This approach is different to that used with the current range of “biological” therapy which targets the main inflammatory mediators, such as tumour necrosis factor alpha (TNF- α). By blocking the abnormal Th1 and Th17 immune events upstream of the inflammatory cascade, APC’s actions would be more comprehensive than current biological treatments as it may subsequently block a range of inflammatory mediators, including TNF-α, interleukin (IL)-1 and IL-17. In addition, APC is known to have few side-effects. Thus, if our hypothesis proves to be correct, APC will provide a wide-ranging and safe therapy for RA with a novel mechanism of action.
There is no cure for arthritis and as the population ages, the burden of arthritis is increasing. The onset of arthritis is usually between the ages of 25 and 50, when people are active in the workplace and in family care roles, so has considerable social and economic costs. This is the International Bone and Joint Decade in which Commonwealth Government of Australia has made arthritis a national health priority. In response to this a National Action Plan has been developed, a key objective of which is to advance knowledge in RA, the most disabling form of arthritis. The knowledge gained from this project is likely to provide direction for new strategies to prevent joint destruction in arthritis. This new science will also provide insights into other diseases affected by similar mechanisms involving abnormal lymphocyte function including a large group of auto-immune and inflammatory diseases such as multiple sclerosis, inflammatory bowel disease and type 1 diabetes.