STRIVE O-GlcNAc : Aurélia Leroux (2024-2027)

Colic is one of the most significant medical and economic health issues in horses, causing substantial financial and sport-related losses due to its high frequency and potential complications. While most cases resolve with medical treatment, around 30% of complicated cases progress to sepsis, which is the leading cause of mortality in horses, with a 40% fatality rate. Sepsis is characterized by a dysregulated host response to infection, leading to systemic inflammation and multi-organ failure. Despite advances in colic management, therapeutic options for equine sepsis remain limited and mostly symptomatic, highlighting the urgent need for innovative treatments.

In the BioSepEq project, our team developed an equine sepsis score similar to that used in humans and identified four dysregulated proteins as potential early biomarkers. We also explored O-GlcNAcylation, a stress-adaptive protein modification shown to have protective effects in septic shock models in rats and mice. Pharmacological enhancement of O-GlcNAcylation significantly reduced mortality in these models. In horses, we demonstrated that blood O-GlcNAc levels decrease progressively during sepsis, supporting the hypothesis that increasing O-GlcNAc levels could improve outcomes.