Wnt, neutrophil extracellular traps emerging as ‘important’ rheumatoid arthritis targets
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SCOTTSDALE, Ariz. — The Wnt signaling pathway, neutrophil extracellular traps and PRIME cells represent “extremely important” emerging targets in rheumatoid arthritis, according to a speaker here.
John R.P. Tesser, MD, FACP, of Arizona Arthritis & Rheumatology Associates and Midwestern University, described the Wnt signaling pathway as a “complicated” and “very interesting intracellular signaling mechanism,” underscoring many organ tissue and cellular activities throughout the body.
“Most people don’t know about the Wnt signaling pathway,” he told attendees at the Basic and Clinical Immunology for the Busy Clinician symposium. “We’re kind of like where we were with JAK signaling back in the early 2000s. Most of us didn’t know what JAK signaling meant until it was identified a target and a drug that came out.”
According to Tesser, research led by Michael B. Brenner, MD, of Harvard Medical School and Brigham and Women’s Hospital, concluded Wnt signatures “are particularly enriched in rheumatoid stromal tissue,” while much less identified in osteoarthritis tissue.
“In the mouse model, they demonstrated that stromal Wnt activation is at peak arthritis times, and that it’s driving the stromal inflammation that we’re seeing,” he said. “They also were able to do some studies where they inhibited Wnt, and they were able to decrease the arthritis severity, thereby concluding, at least in the mouse model, that Wnt regulation and regulating the inflammatory pathology in these fibroblasts may have significant therapeutic potential as a target in rheumatoid arthritis.”
Tesser additionally characterized neutrophil extracellular traps (NETs) as a “hot item” in lupus research. He shared results from a study finding decreased NET activity following treatment with either a standard disease-modifying antirheumatic drug, abatacept (Orencia, Bristol Myers Squibb), a TNF inhibitor or an interleukin-6 inhibitor, suggesting NETs are “important in inflammation and malleable to our therapeutic devices.”
“We’re going to see more on NETs,” Tesser added. “I will tell you I’ve had a conversation with a company that is looking at dissolving NETs as a therapeutic target, and we’ll see what we get from that.”
Tesser also named PRIME cells as a potential therapeutic target, describing them as “more-recently focused-on mesenchymal cells that apparently are very important helping to flare the disease.”
“There’s been an association of increasing circulating PRIME cells with flares of clinical disease,” he said. “And now there’s some new ways of trying to identify methods to inhibit those cells if possible.”
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Tesser JRP. Beyond TNF Blockade: Breakthroughs in Rheumatoid Arthritis Pathogenesis. Presented at Basic and Clinical Immunology for the Busy Clinician, Feb. 17-18, 2024; Scottsdale, Arizona (hybrid meeting).
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