Published in Journal of Clinical Investigation
Scientists learn more every day about how different genes, cells, and chemicals within the body interact and contribute to synovial inflammation and joint destruction, bringing us closer to finding new treatments and cures for rheumatoid arthritis (RA). Two recently published case reports intrigued some scientists.
One report was of a person with RA and chronic myelogenous leukemia. The other report was of a person with RA and gastrointestinal stromal tumors. Their cancers were treated with imatinib mesylate. In both cases, the people experienced improvement in the pain and inflammation in their joints. Was the cancer treatment also treating their RA, wondered scientists.
What problem was studied?
The cancer drug imatinib mesylate (Gleevec) potently inhibits tyrosine kinases, enzymes that act as the “on” switch for various cells. For example, a tyrosine kinase turns on pancreatic cells so that they start making insulin. Imatinib specifically targets certain tyrosine kinases that are involved in cancer growth.
Because several of the tyrosine kinases that are involved in cancer are also involved in RA, and because those intriguing case reports indicated a possible therapeutic benefit for RA patients, researchers decided to investigate imatinib mesylate as a potential treatment for RA.
A team from Stanford University School of Medicine and the Palo Alto VA Health Care System in California, led by Arthritis Foundation-funded researcher William H. Robinson, MD, PhD, and joined by Arthritis Foundation-funded Stanford researcher Paul J. Utz, MD and others from Harvard Medical School in Boston, investigated the efficacy and mechanisms of action of imatinib in a mouse model of RA called collagen-induced arthritis (CIA).
What was done in the study?
Mice that are genetically susceptible to developing CIA were injected with collagen to induce inflammatory arthritis. Some mice were treated with imatinib before collagen injection, some were treated after clinical arthritis was established, and others received no imatinib and acted as the control group. Along with assessing clinical and microscopic evidence of arthritis, scientists also measured various chemical levels in the blood and joints to help determine the mechanism of action of the drug.
What were the results?
Imatinib was effective at preventing arthritis in the mice who received the drug before the collagen injection; it also was effective at treating established arthritis. Results of the team’s chemical analyses showed that the drug acted by selectively inhibiting a variety of chemical pathways central to the development of RA.
What does this mean to people with autoimmune disease?
The results of this experiment open the door to investigate imatinib mesylate as a potential treatment for RA. Furthermore, identifying the chemical pathways affected by this drug lead researchers to believe that imatinib may be of benefit in other autoimmune diseases, such as Crohn's disease, psoriasis and multiple sclerosis. In particular, one mechanism of action disrupts a pathway that results in fibrosis, leading researchers to believe that imatinib may be of benefit in scleroderma and idiopathic pulmonary fibrosis.
Paniagua RT, Sharpe O, Ho PP, et al. Selective tyrosine kinase inhibition by imatinib mesylate for the treatment of experimental arthritis. J Clin Invest 2006. Published online ahead of print September 14, 2006.