Inhibition of VEGF-A, P2RX7 or the combination of FLT1 and VEGFR-2 to treat tuberculosis

INDICATION: Tuberculosis

Mouse studies suggest inhibiting VEGF-A, P2RX7 or the combination of FLT1 and VEGFR-2 could help treat tuberculosis (TB). In a mouse model of TB, expression of mutant VEGF-A with reduced binding to its receptor or induction of VEGF-A in monocytes via myeloid-specific knockout of VEGF-A or P2RX7 decreased the number of granulomas and granuloma leukocytes compared with normal expression of VEGF-A and P2RX7. Also in the model, a mAb targeting VEGF-A, a tool compound P2RX7 antagonistor a tool compound dual inhibitor of FLT1/VEGFR-2 decreased the number of granulomas and granuloma leukocytes compared with vehicle. In a second mouse model of TB, myeloid-specific VEGF-A knockout decreased lung inflammation and increased survival compared with normal VEGF-A expression. In the same model, the FLT1/VEGFR-2 inhibitor decreased lung inflammation compared with vehicle. In a third mouse model of tuberculosis that forms caseating human-like lung granulomas, the FLT1/VEGFR-2 inhibitor decreased the number of large, dense granulomas. Next steps could include testing approved VEGF-A inhibitors in patients with TB...