Acute inflammation is normally followed by a resolution phase that protects tissue from the harmful effects of chronic inflammation. Once thought to be passive, resolution is now known to be actively regulated by endogenous lipid autacoids known as resolvins.
Resolvin E1 (RvE1), the active moiety in Thetis’ lead candidate, TP-317, is synthesized within inflamed tissue and acts locally to induce inflammation resolution. Therapeutic administration of TP-317 is associated with anti-inflammatory and mucosal healing effects in multiple models of inflammatory bowel disease (IBD).
Separate studies have demonstrated the ability of RvE1 to modulate cellular and molecular mechanisms implicated in IBD, including immune cell activation and trafficking and inflammatory cytokine signaling. RvE1 has also been shown to promote tissue repair and re-epithelialization, suggesting a role in mucosal healing. Finally, TP-317 also activates regulatory T-cells, suggesting an ability to enhance immunological tolerance. Together, these findings support further investigation of TP-317 as a novel IBD therapy.
Source: Wang and Colgan. Mol Aspects Med. 2017.