Cancer Drug May Be Remedy for Rheumatoid Arthritis

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

Thursday September 28, 12:29 pm ET

STANFORD, Calif.--(BUSINESS WIRE)--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 visiting undergraduate Fiona .

Stanford University Medical Center integrates research, medical

education and patient care at its three institutions -- Stanford

University School of Medicine, Stanford Hospital & Clinics and Lucile

Packard Children's Hospital at Stanford. For more information, please

visit the Web site of the medical center's Office of Communication &

Public Affairs at http://mednews.stanford.edu.

NOTE: Reporters may download a copy of the paper, which has been

posted in advance of publication, by visiting http://www.jci.org and

searching the site using the term " imatinib mesylate. "

Contact:

Stanford University Medical Center

Mitzi Baker, 650-725-2106 (Print Media)

mabaker@...

M.A. Malone, 650-723-6912 (Broadcast Media)

mamalone@...

Source: Stanford University Medical Center