Scientists stumble on potential arthritis drug target

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Scientists stumble on potential arthritis drug target

16/02/2006- Scientists exploring inflammation in rheumatoid arthritis

have made an unexpected discovery that may lead to new drug

treatments to ease the pain and discomfort endured by 66 million

(nearly 1 in 3 adults) US citizens in 2005.

Although there's no known cure for the stiffness, swelling, joint

pain, and fatigue of rheumatoid arthritis, millions of people who

live with the disease now receive better diagnoses and have access to

new medications.

Rheumatoid arthritis (RA) is a chronic autoimmune disease

characterised by inflammation of the lining, or synovium, of the

joints. It is one of the most severe forms of arthritis and can lead

to long-term joint damage, resulting in chronic pain, loss of

function and disability. RA affects 1 per cent of the US population

or 2.1 million Americans, mostly women.

Researchers at the Joslin Diabetes Centre and Massachusetts General

Hospital (MGH) in Boston, developed a new microscopic imaging method

to visualise changes in blood vessel permeability in anaesthetised mice.

Within minutes following the delivery of arthritis-causing antibodies

to the mice, the blood vessels around the joints became temporarily

leaky, making it easier for the antibodies to enter the joint spaces.

There, the antibodies set off a cascade of inflammatory cells and

molecules, eventually resulting in arthritis.

The researchers isolated histamine, a small molecule usually

associated with asthma and allergy, as central to the part of the

inflammatory process that occurs during the development of arthritis.

Histamine made the blood vessels surrounding the joints especially

vulnerable to leakage, and thereby rendered the joints more

susceptible to inflammatory attack.

The researchers believe that this is true not only in rheumatoid

arthritis, but perhaps also in other autoimmune conditions with which

arthritis is associated, such as lupus, and in some infectious

diseases, like Lyme disease.

“For patients with rheumatoid arthritis, these new findings raise the

possibility that medications designed to prevent the blood vessels

from becoming leaky might one day be used to delay the onset of

arthritis or to prevent flare-ups of disease,” said Christophe

Benoist, who led the study.

While the Joslin lab focuses its work on type 1 diabetes, arthritis

has several related mechanisms. Like type 1 diabetes, rheumatoid

arthritis is an autoimmune disease, in which the body’s immune system

attacks itself as though fighting off an enemy invader.

“The big surprise was that the other blood vessels throughout the

body did not become leaky, suggesting that there is something special

about the vessels in the joints,” says Bryce Binstadt, of Joslin and

Children’s Hospital Boston, lead author on the study.

The report appeared in the January 29 online issue of Nature

Immunology, and is scheduled to appear in the March print edition.

http://www.drugresearcher.com/news/printNewsBis.asp?id=65884