Infectious disease

Patient sample, cell culture and mouse studies suggest inhibiting VEGF-A, VEGFR-2 or HIF1 could help treat Clostridium difficile infection (CDI). In serum samples from patients, levels of VEGF-A were higher than in samples from healthy volunteers. In a mouse model of CDI, an mAb targeting VEGF-A or a tool compound inhibitor of its receptor VEGFR-2 decreased vascular permeability in the colon and cecum and weight loss, and increased survival compared with a control IgG or vehicle, respectively. Also in the model, intestinal epithelium-specific knockout of HIF1, a positive regulator of VEGF-A, delayed onset of diarrhea and decreased weight loss compared with normal HIF1 expression. Next steps could include testing VEGF-A, VEGFR-2 and HIF1 inhibitors in other models of CDI.

Japan Tobacco has the HIF1 inhibitor JTZ-951 in Phase II testing for anemia. ...