△ Schematic illustration showing the suppression of key pathogenic cells driving joint destruction in rheumatoid arthritis

A research team led by Professor Seung-Ah Yoo (Department of Biomedical Science, College of Medicine, The Catholic University of Korea) and the Center for Creative Systemic Medicine, in collaboration with the biotech company GBIOLOGICS (CEO Dong-Ho Song), has unveiled a promising new therapeutic approach for rheumatoid arthritis (RA). The study was published in the prestigious international journal Molecular Therapy (Impact Factor: 12).

The research was conducted by Professors Seung-Ah Yoo and Wan-Uk Kim (co-corresponding authors), Dr. Mi-Ryung Lee and Dr. Min-Kyung Nam (co–first authors), along with a multidisciplinary team. Using both patient-derived tissues and animal models, the team provided strong experimental evidence for a novel treatment mechanism.

Rheumatoid arthritis is an autoimmune disease in which the immune system mistakenly attacks the body’s own tissues, particularly the synovium, the thin membrane surrounding the joints. This leads to chronic inflammation that eventually destroys cartilage and bone. Existing therapies mainly target inflammatory signals or overactive immune cells, but persistent aggressiveness of fibroblast-like synoviocytes (FLSs) within joints has hindered complete recovery.

By applying single-cell transcriptome analysis, the researchers identified—for the first time worldwide—a particularly aggressive subtype of synovial cells in RA patients, characterized by abnormally high production of macrophage migration inhibitory factor (MIF). They named these cells MIF-high FLSs.

These cells showed mitochondrial and endoplasmic reticulum dysfunction, causing excessive proliferation, migration, and joint-destructive behavior. To counteract this, the team used recombinant stabilized Galectin-9, developed by GBIOLOGICS, which naturally regulates immune and inflammatory responses in the body.

Galectin-9 effectively blocked the MIF–CD74/CD44 signaling pathway, turning off the “self-activation switch” that drives synovial cell aggression. As a result, cell proliferation, migration, and invasion were significantly suppressed, and joint destruction was visibly reduced.

In SCID mouse models transplanted with human RA tissue and collagen-induced arthritis (CIA) models, Galectin-9 prevented cartilage and bone damage while alleviating arthritis symptoms, demonstrating potent therapeutic efficacy at the preclinical level.

Unlike existing drugs such as Enbrel or Tofacitinib, which mainly suppress inflammation or immune cells, Galectin-9 directly targets the core pathogenic cells—the synovial fibroblasts responsible for joint damage. Even in patients who achieve clinical remission, these cells often remain active, leading to ongoing damage. This study presents a novel strategy to overcome that limitation.

Professor Yoo stated, “Our findings confirm the potential to directly suppress the fundamental pathogenic cells of rheumatoid arthritis. We will continue efforts to translate this into clinical research for patient treatment.”
 Professor Kim added, “Rheumatoid arthritis requires lifelong management, but this cell-targeted approach marks a major step forward both scientifically and clinically.”

△ Prof. Seung-Ah Yoo, Prof. Wan-Uk Kim, Dr. Mi-Ryung Lee, and Dr. Min-Kyung Nam