New Targeted Therapy to Treat Inflammatory Bowel Disease

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“It is why it is targeted by drugs. Our interest in this study was to look for a more targeted therapy that might have a better impact than the existing approach, which is to block all TNF-alpha,” Lo added.

The researcher explained that people have two different receptors, TNFR1 and TNFR2, in each of their cells that bind TNF-alpha. Currently, TNF-alpha-targeted drugs block both TNFR1 and TNFR2.

Lo’s experiments were done in mice, which have the same two receptors. The pattern of inflammation in mice is similar to that seen in humans.

TNF-alpha, produced by the body’s cells, also induces specialised immune and other cells, which both promote inflammation and suppress it. Thus, TNF-alpha plays a role in the destruction and the healing of tissues, a double-edged sword.

Lo said evidence exists that TNFR1 may be driving most of the destructive effects of IBD, whereas TNFR2 may drive the healing and restorative effects.

“If you block both the receptors, you block the destructive effects and the recovery,” he said. “To circumvent this, in our work we opted to do selective targeting of TNFR1.”

Lo’s group was encouraged by two pieces of evidence suggesting that targeting TNFR1 may be a more beneficial strategy.

The researchers used a reagent from a biotechnology company, that was selective for blocking TNFR1.

Mice treated with this reagent were found to benefit from it. The researchers also did genetic targeting of TNFR1 to reduce its signaling. The impact, they found, was dramatic.

“When we reduced TNFR1 signaling, the mice showed a significant benefit relative to mice who had the full level of TNFR1 signaling,” Lo said.

“This approach may offer more opportunity to TNFR2 to contribute to the healing.”

Source: IANS



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