Mouse Model Mimics Human RA in Late Stages
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. In the past, RA patients were often grossly undertreated since the available treatment options could be very toxic. A decade ago, anti-TNF therapy was considered a real breakthrough in the management of RA. However, this treatment has many shortcomings and a substantial portion of the RA patients do not benefit from the treatment.
Dr. Cham’s lab has developed a new mouse model of inflammatory arthritis — an improved humanized arthritis model of RA. These mice closely mimic both the acute and the chronic progressive phases of RA in humans and can eventually develop manifestations outside of the joints, often seen in human RA patients in late stages of disease. Dr. Cham introduced the enzyme luciferase as a transgene in these mice. When they are given a small dose of the photochemical luciferin (a chemical which enables fireflies to glow in the dark), sites of inflammation (i.e., joints or lungs) will become illuminated. Lighted images can be detected and digitally captured on camera. The luciferase transgene will be a powerful tool to visually follow the progression of disease inside of the same animal.
The new mouse model will also be ideal for pre-testing new treatments for RA patients. The cytokine IL-17 has been associated with RA in humans. Using the new mice, Dr. Cham plans to test whether blocking IL-17 will reduce the destructive processes often seen in the later stages of disease. If so, targeting IL-17 would be a promising new strategy in the fight against RA.