Scientists stumble on potential arthritis drug target
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.
