New humanized mouse model of chronic rheumatoid arthritis in humans
In rheumatoid arthritis (RA), the immune system attacks and damages the individual’s own joints. RA is characterized by episodes of acute inflammation, followed by long periods of smoldering disease with chronic joint pain and slow but progressive cartilage and bone destruction, eventually leading to loss of joint function. Recently, significant progress has been made in understanding the underlying causes of RA. The cytokine IL-17 has been implicated in the pathogenesis of RA, particularly with respect to bone erosions. Furthermore, a subtype of T cells (Th17 cells) has been found to produce abundant amounts of IL-17. These observations make IL-17 an exciting new target for the treatment of severe RA.
During the past year Dr. Cham has demonstrated that her humanized mouse model of RA develops a very severe arthritic disease which persists even after the acute phase of inflammation has subsided. By using imaging tools, areas of inflammation could be seen specifically in the paws of arthritic mice. In the coming year, she plans to use the humanized mouse model of RA to test a potential biological therapeutic, anti-IL-17. She will compare the efficacy of anti-IL-17 treatment with anti-TNF therapy (a well-tested therapy for RA) by evaluating the following: 1) how well anti-IL-17 controls inflammation in established disease and 2) whether anti-IL-17 blocks destructive bone erosions seen in the later stages of disease.