Gleevec May Be Remedy for Rheumatoid Arthritis

[Guest guest]

http://www.docguide.com/news/content.nsf/news/852571020057CCF6852571F800

49DF61

Cancer Drug May Be Remedy for Rheumatoid Arthritis, Stanford Study Finds

STANFORD, CA -- September 29, 2006 -- The potent cancer drug Gleevec,

used to combat leukemia and some gastrointestinal cancers, may be useful

in treating rheumatoid arthritis, according to a team of researchers at

the Stanford University School of Medicine.

Their findings will be published in the October issue of the Journal of

Clinical Investigation.

Although the study shows that Gleevec worked well in mice, the

researchers cautioned against doctors using Gleevec for treating

rheumatoid arthritis until clinical trials are completed demonstrating

its effectiveness and safety for people with the disease.

Rheumatoid arthritis is a painful, chronic autoimmune disorder,

characterized by inflammation of the lining of the joints. It affects

more than 2 million Americans; up to half of those with the disease are

disabled after 15 years due to disfigured joints. Standard therapy for

rheumatoid arthritis now includes agents that suppress the immune

system, but many patients do not benefit from such treatments. They do

not get adequate reduction in the symptoms and signs of disease; they

may also continue to have damage to their joints or develop side effects

that make continued use of such therapies impossible. Thus, new

approaches are needed.

Bill , MD, PhD, assistant professor of medicine and the study's

senior author, led a team that set out to find drugs that might provide

additional benefit to rheumatoid arthritis patients. They screened a

range of drugs in mice that have a condition similar to human rheumatoid

arthritis.

Paniagua, an MD/PhD student and the study's first author,

explained that they looked at every drug approved by the U.S. Food and

Drug Administration, considering which ones might modulate the immune

system and thus be effective in combating an autoimmune condition,

regardless of the drug's FDA-approved use. Paniagua chose several drugs

to test, including an antihistamine, a platelet modulator and other

approved drugs with known effects on cells of the immune system.

" It was the combination of rational selection and serendipity that we

found that Gleevec worked better than anything else, " said Paniagua, who

works in 's laboratory at the Geriatric Research, Education and

Clinical Center of the Palo Alto Veterans Affairs Health Care System.

In their study, Gleevec almost completely prevented the development of

the rheumatoid arthritis-like disease in the mice. The drug also halted

the progression of established disease, significantly reducing the

amount of inflammation and bone destruction around the joints. The

researchers also tested Gleevec on the cells of human rheumatoid

arthritis patients and found that it reduced the processes associated

with inflammation and abnormal growth in the joints.

Gleevec is the brand name of imatinib, a drug produced by the

pharmaceutical company Novartis AG. It is part of a class of drugs

called kinase inhibitors, which act by blocking communication signals

between cells. These signals, when they go awry, are often at the root

of diseases such as cancer and autoimmune conditions.

Gleevec targets kinase gene mutations seen in chronic myelogenous

leukemia or CML (a bone marrow cancer) as well as certain types of

stomach cancers. The same kinases turn out to play a critical role in

rheumatoid arthritis.

said that the field of autoimmune disease research has been

trying to develop kinase inhibitors for more than a decade. " We were

very surprised that Gleevec worked as well as it did, " said .

" It just seemed too simple. " The results are especially encouraging

since the drug is already FDA-approved, and has relatively few side

effects. None of the authors in the study has any affiliation with

Novartis.

" We have taken a very potent kinase inhibitor and discovered that it

works very well for an autoimmune disease, " said . " The

significance is twofold. First, it might provide insights into the

mechanisms underlying rheumatoid arthritis by figuring out what Gleevec

inhibits. " Second, he added, it might represent a new therapeutic

approach to rheumatoid arthritis and other autoimmune diseases. The

kinases the drug inhibits likely play a role in other autoimmune

diseases, such as scleroderma, psoriasis and inflammatory bowel disease.

Gleevec's potential in humans is buoyed by two published case studies of

rheumatoid arthritis patients with CML; both experienced significant

improvements in their arthritis symptoms after taking Gleevec to treat

their cancer. In addition, there has been a published case study of

Gleevec alleviating psoriasis in a cancer patient. said he

hopes that in the near future, clinical trials will be conducted that

look at the drug's effectiveness for a range of autoimmune diseases.

Others who contributed to the study are associate professors of medicine

Mark Genovese, MD, and Utz, MD; professor of orthopedic surgery

Stuart Goodman, MD; assistant professor of pathology Higgins, MD;

professor of neurology and neurological sciences and of pediatrics

Lawrence Steinman, MD; research associate Peggy Ho, PhD; research

assistants Orr Sharpe, MS, and Beren Tomooka, MS; MD/PhD student

Chan; medical fellow Song, MD; Stanford undergraduate Chang,

and visting undergraduate Fiona .

SOURCE: Stanford University Medical Center