New Arthritis Treatment Could Slow Joint Damage
/By Pat Anson, Editor
Researchers in California are working on a novel method for the treatment of rheumatoid arthritis that could open the door to a new class of medications that prevent joint damage.
Rheumatoid arthritis (RA) is a chronic autoimmune disease in which the body’s own defenses attack joint tissues, causing pain, inflammation and bone erosion. Most RA treatments focus on suppressing the immune system to reduce inflammation and slow progression of the disease.
"Unfortunately, for around 40 percent of patients, immune-targeted therapies are not sufficient to bring them into full remission," said Nunzio Bottini, MD, an associate professor at the La Jolla Institute for Allergy and Immunology and associate professor of Medicine at the University of California, San Diego.
"If we could add a drug that acts on a different target without increasing immune suppression it could be very valuable."
Bottini and his colleagues are focusing on specialized cells called fibroblast-like synoviocytes (FLS) that line the inside of joints, providing lubrication and repairing joint injuries. In RA patients, the cells invade surrounding cartilage and secrete enzymes that break down the rubbery tissue that cushions the bone. They also trigger bone destruction.
"Even if your inflammation is completely under control with the help of current therapies -- and they are excellent -- the damage to the skeletal structure is not necessarily arrested in the long term because synoviocytes continue to cause damage," explains Bottini. "And although synoviocytes are considered the main effectors of cartilage damage in rheumatoid arthritis there's no therapy directed against them."
FLS cells rely on phosphates to transmit signals. When researchers screened tissue samples from rheumatoid arthritis patients for the expression of phosphatases, they discovered that an enzyme called RPTPσ -- short for receptor protein tyrosine phosphatase sigma -- is highly expressed on the surface of their FLS cells. RPTPσ weakens the ability of synoviocytes to aggressively invade the joint's cartilage.
"RPTPσ acts like an inhibitory signal that is pre-coded on the surface of these cells," says postdoctoral researcher Karen Doody, PhD, first author of the study published in Science Translational Medicine.
“Being able to activate RPTPσ's activity gives us a specific tool with which to adjust the migration and aggressiveness of synoviocytes in rheumatoid arthritis," said Doody, who hopes to develop drugs that make the cells less invasive and lose their ability to attach to cartilage.
"The ultimate goal is to use biologics that target synoviocytes in combination with treatments that suppress the immune system, such as methotrexate or anti-TNF, to address all three aspects of rheumatoid arthritis: swollen joints as a result of inflammation, cartilage damage and bone damage."
About 1.5 million Americans and 1% of adults worldwide suffer from RA.
