New Treatment Target Found for Rheumatoid Arthritis

Novel drug target found in cells directly responsible for cartilage damage in affected joints.

The discovery of cells that are responsible for cartilage damage in joints affected by rheumatoid arthritis presents a promising new drug target for the disease, a recent study found.

Published in the May 20, 2015 issue of Science Translational Medicine, the discovery could lead to a new class of medications that prevent joint damage in patients who don't respond to current treatment regimens. These treatments typically seek to block the immune system from attacking the lining of affected joints to decrease inflammation and slow disease progression.

"Unfortunately, for around 40% of patients, immune-targeted therapies are not sufficient to bring them into full remission," lead author Nunzio Bottini, MD PhD, said in a press release. "If we could add a drug that acts on a different target without increasing immune suppression it could be very valuable."

The inflammatory process in rheumatoid arthritis activate fibroblast-like synoviocytes (FLS), which are specialized cells lining the inside of joints to provide lubrication and to repair injured joints. When these cells mobilize, the FLS invade surrounding cartilage and secrete enzymes that break down the tissue that provides cushion for the bone, while also triggering 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," Dr. Bottini said. "And although synoviocytes are considered the main effectors of cartilage damage in rheumatoid arthritis there's no therapy directed against them."

FLS behavior is guided by intracellular signaling cascades, which are dependent on small phosphate groups to transmit signals through the cell. The phosphate groups are attached to proteins by kinases, the study noted.

By changing the phosphorylation status of a signaling molecule triggers specific changes in molecule activation status. The researchers found an enzyme called RPTPσ that is highly expressed on the surface of FLS and can be activated to block damage to joint cartilage.

"The unique aspect of this approach is the ability to improve symptoms and decrease joint damage while potentially avoiding any negative effects on normal immune responses and susceptibility to infections," co-author Gary S. Firestein, MD, said in a press release.