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A new treatment targeting tenascin-C could reduce the progression and severity of rheumatoid arthritis (RA) at the very early stages of disease.

RA is a common and debilitating disease affecting over 400,000 people in the UK. Current treatments, whilst effective for some people with RA, can lead to side effects and a comprised immune system. Moreover these drugs are not effective at all in many people. The condition causes joint swelling, stiffness and pain, and can lead to devastating destruction of joint tissue.

This selective approach might offer a safer treatment alternative to global immune suppression for people with RA.

Researchers from the Kennedy Institute, University of Oxford have found that a protein from the cell’s matrix, tenascin-C, is not present in the outer covering of healthy joints – an area known as the synovium – but that it appears in people who develop RA even before disease diagnosis. Using an innovative approach, the team have targeted tenascin-C for the first time and were able to reduce the progression and severity of RA in the lab.

Lead researcher Professor Kim Midwood says: "We previously identified tenascin-C as an endogenous trigger of the immune response. Normally kept under strict control, high levels of this protein accumulate in the joints of people with RA, driving chronic inflammation. Tenascin-C is a huge protein that has lots of different binding partners. Our lab mapped the exact region in tenascin-C responsible for its ability to activate the immune system, and which contributes to inflammation in RA. This enabled us to work together with Nascient Ltd to design and test drugs that prevent this part of tenascin-C from triggering inflammation. These drugs were engineered to be extremely specific; they only stop inflammation driven by tenascin-C and leave intact our ability to fight off infection. This selective approach might offer a safer treatment alternative to global immune suppression for people with RA."

She adds: "Working together with the team at Birmingham also enabled us to examine synovial biopsies from people with early RA. This revealed that tenascin-C appears much earlier during disease development than we previously thought; providing a potentially very exciting avenue for very early treatment of RA."

These promising results for RA sufferers have also been causing a stir in the academic community. Until now, tenascin-C had evaded researchers from becoming a potential therapeutic target due a lack of drugs that specifically block the pro-inflammatory action of this large multifunctional matrix molecule. With this research, the team at the Kennedy have managed to rein tenascin-C in for the first time and use it as a disease specific target.

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