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A cure for Rheumatoid arthritis

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According to a new research, first published on Sep 8, 2014 in the Journal of Immunology, researchers have discovered that deactivating the toll-like receptor 5 (TLR5) cell protein can halt the progression of rheumatoid arthritis. TLR5 is found on myeloid cells which migrate from the blood into joints where the disease takes place. The study reports that TLR5 is either a parallel or more upstream regulator than TNF-alpha, which is already a well-established therapeutic target.

Professor Shiva Shahrara and her research team at the University of Illinois at Chicago College of Medicine have discovered that blocking TLR5 seems to stop the cycle of inflammation and bone erosion in rheumatoid arthritis. The results suggest a new and significant target for therapy.

The research team first found that the receptor is more highly expressed in myeloid cells in the joint fluid of patients with the disease compared to non-RA individuals. Next, the researchers showed that myeloid cells with TLR5, when incubated next to synovial fluid from RA patients, migrated into the fluid due to attraction to a yet-unknown factor in the synovial fluid. Blocking the receptor diminished the migration.

The researchers then incubated the myeloid cells with TLR5 in synovial fluid and found that TNF-alpha, an inflammatory molecule that attracts more myeloid cells to the joints, was produced. The finding is very important because a successful existing therapy for RA infliximab is designed exactly to soak up TNF-alpha. Interestingly, patients who take anti-TNF-alpha medication have been shown to have reduced levels of TLR5, suggesting that there is feedback from TNF to TLR5, and that the causality of events is not unidirectional.

The two experiments established that TLR5 attracts myeloid cells that result in bone degradation both directly and indirectly.

Working with a culture of myeloid cells immersed in joint fluid, the researchers found that either anti-TNF-alpha or anti-TLR5 reduced the number of osteoclasts formed in comparison to untreated cells by 40% and 50% respectively. But more interestingly, a combination of the two synergistically reduced the osteoclast count by about 70%.

To show greater clinical relevance, the researchers turned to a mouse model of RA, and blocked TLR5 with an antibody to show that it had a strong effect on reducing swelling and bone erosion. Detailed testing revealed that there were less myeloid cells drawn to the joint, and reduced generation of osteoclasts compared to mice that received instead a generic IgG antibody.

Results of the Study

Professor Shahrara and her team have inferred that a clinically safe drug that blocks TLR5 activation has the power to decelerate or stop inflammation and bone degradation altogether. The drug could work either alone, or in combination with anti-TNF therapy.

“When TLR5 is activated, it initiates a vicious feedback loop that results in a worsening of both the inflammatory and erosive features of rheumatoid arthritis,” Shahrara explains. “The receptor is a major driver of inflammation and bone degradation. Blocking this receptor could have significant therapeutic value in interrupting joint swelling and bone loss in patients with rheumatoid arthritis.”

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This web site is run by an Arthritis Specialist based in Dubai, United Arab Emirates. On this site you will find news about the latest in arthritis, information about research results in the field, tips and information and diet and exercise, and much more.

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