SUMOylation as a therapeutic target in inflammatory bowel diseases and sepsis

Unmet Need

Inflammatory Bowel Disease (IBD) affects between 2.4 – 3.1 million people in the USA alone, with significant risks of complications such as sepsis. Chronic inflammation from IBD results in severe intestinal tissue damage, potentially leading to systemic infections and organ failure. While immunosuppressive drugs like anti-TNFα therapies can help, they are costly, and many patients experience a loss of efficacy and harmful side effects. There is a critical need for novel IBD treatments to address sepsis and related complications effectively.

Technology

Duke inventors have developed a novel approach for the treatment and prevention of inflammatory disorders through the administration of SUMOylation inhibitors. This is intended to be used by physicians in lieu of existing immunomodulatory treatments for IBD. Specifically, Duke inventors have identified that small ubiquitin-like modifier (SUMO) compounds, such as TAK981, can be used as effective treatments for IBD and sepsis. TAK981, a SUMO inhibitor, modulates key cytokines IFNγ and TNFα, showing improvements in colitis symptoms and inflammation in vivo in mouse models. This has been demonstrated in mouse models of polymicrobial peritonitis, a common indicator of sepsis onset, in which TAK981 increased survival rates and immune responses. This technology offers a selection of SUMOylation inhibitors beyond TAK981, expanding therapeutic options.

Advantages

• Modulates the immune system, lowering the likelihood of resistance development.
• Potential to significantly improve patient outcomes in inflammatory diseases.
• Addresses unmet needs by providing an alternative to current immunosuppressive and immunomodulatory treatments.
• Offers a targeted approach with a range of SUMOylation inhibitors, including TAK981.