RESEARCH - Imatinib mesylate (Gleevec) as a potential treatment for RA

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Arthritis Foundation

Research Summary:

Imatinib as Treatment for Experimental Arthritis

Published in Journal of Clinical Investigation

September, 2006

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 H. , MD, PhD, and joined by Arthritis

Foundation-funded Stanford researcher 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

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