Hench Lecture to Review Synovial Fibroblast Research in Pursuit of RA Therapies that Won’t Suppress the Immune System

Synovial fibroblasts are nonimmunological cells that can become destructive and contribute to rheumatoid arthritis (RA) by amplifying inflammation and promoting damage to bone and cartilage. But what if these local cells that line the inside of joints and help them move could be mined for target therapy to treat the disease without suppressing the immune system?

Nunzio Bottini, MD, PhD, Professor of Medicine at Cedars Sinai Medical Center and Director of the Cedars-Sinai Kao Autoimmunity Institute, will discuss these possibilities and more during this year’s Hench Memorial Lecture on Sunday, Nov. 17, from 1–2 p.m. ET in Room 145AB of the Walter E. Washington Convention Center. The lecture, Synovial Fibroblasts in Rheumatoid Arthritis: Searching for Targetable Mechanisms, will cover the latest research on fibroblasts as potential cellular targets for disease control. The session will be available on demand within 48 hours for registered ACR Convergence 2024 participants.

While there are no U.S. Food and Drug Administration (FDA)-approved drugs for RA that target synoviocytes, cells involved in producing synovial fluid, researchers continue to look for good targets.

“I will provide an outline of the previously established role of synovial fibroblasts and highlight the discoveries in the last five years that have brought these cells to the spotlight, making the case of why targeting them would solve unmet needs in RA, and then discuss the cutting edge of investigations,” Dr. Bottini noted.

In his lecture, Dr. Bottini will showcase contributions of various research teams, review work undertaken by his own lab, and look at historical attempts to target synovial fibroblasts for new RA therapies.  

A recent development in research indicates that multiple subsets of synoviocytes exist in the joints, including some that can reduce rather than promote inflammation.

“Now we have access to genomic data about synovial fibroblasts from multiple patients,” Dr. Bottini said. “We realize the diversity of subsets, and that data could be useful in the search for new targets.”

For example, Dr. Bottini said the data might help determine whether investigators can find targets on these cells that would allow them to inhibit only the function of pathogenic subsets in a way that would not necessarily alter the function of other fibroblasts in the body.

There is also ground-breaking data that suggest that synovial fibroblast-like cells might circulate in the blood of some patients, Dr. Bottini noted. It raises questions regarding how these circulating cells impact disease mechanisms or may be leveraged for diagnosis.

Synovial fibroblasts play a critical role in RA but have remained understudied until the last five years, according to Dr. Bottini. The possibility that continued research might lead to non-immunosuppressive and joint localized therapy approaches is of great interest to rheumatologists and their patients.

“Targeting synovial fibroblasts is one of the potential avenues to accomplish those valuable objectives,” he said.