Researchers Identify Novel Rheumatoid Arthritis Therapy Target

The cells directly responsible for cartilage damage in rheumatoid arthritis might be a viable novel drug target for treatment.

The cells directly responsible for cartilage damage in rheumatoid arthritis (RA) might be a viable novel drug target for treatment, according to research published in Science Translational Medicine.

Researchers from the La Jolla Institute for Allergy and Immunology aimed to identify a viable target for RA drug therapy. The researchers noted that there are several therapies available for RA which target the immune system, but many RA patients do not achieve remission. Specifically, joint lining cells called fibroblast like synoviocytes (FLS) become activated during RA and mediate joint inflammation and destruction of cartilage bone, the researchers said.

"Unfortunately, for around 40 percent of patients, immune targeted therapies are not sufficient to bring them into full remission,” explained lead author Nunzio Bottini, MD, PhD, associate professor at La Jolla Institute 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.”

The researchers found RPTPσ, which is a transmembrane tyrosine phosphatase, as a viable target for FLS directed therapy. One of the mechanisms that regulates RPTPσ also regulates FLS function, the researchers determined.

“Our data demonstrate that FLS are regulated by an RPTPσ dependent proteoglycan switch in vivo, which can be targeted for RA therapy,” the authors concluded. “We envision that therapies targeting the proteoglycan switch or its intracellular pathway in FLS could be effective as a monotherapy or in combination with currently available immune-targeted agents to improve control of disease activity in RA patients.”

The next step for the researchers is to test RPTPσ in preclinical models, especially in combinations with other RA treatments to result in more efficacious therapies.

“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 RA: swollen joints as a result of inflammation, cartilage damage and bone damage,” said Bottini. “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. And although synoviocytes are considered the main effectors of cartilage damage in RA there's no therapy directed against them.”