Therapeutics: Glycolysis, gluconeogenesis and glutamine metabolism pathways
Mouse studies suggest a combination of inhibitors of glycolysis, gluconeogenesis and glutamine metabolism could help prevent heart transplant rejection. The combination comprised the glycolysis inhibitor 2-deoxyglucose, the hepatic gluconeogenesis inhibitor generic metformin and the glutamine metabolism inhibitor 6-diazo-5-oxo-L-norleucine. In a mouse model of ovalbumin-specific CD8+ T cell responses, the combination decreased ovalbumin-specific cytotoxic T cell responses, secretion of interferon γ, the ratio of effector T cells to Treg cells, and other markers of T cell-mediated transplant rejection compared with vehicle. In a mouse model of allogeneic heart transplant rejection, the combination decreased necrosis, fibrosis, and lymphocyte infiltration in the heart and increased survival compared with vehicle. Next steps could include testing the combination in additional animal models of organ transplant rejection...