Inflammation
Mouse studies suggest down-regulating catecholamines with NPPA or the TYH inhibitor Demser could help treat CRS. In a mouse model of colon cancer with Clostridium novyi-NT-induced CRS, C. novyi-NT engineered to express NPPA decreased plasma levels of catecholamines and cytokines and myeloid cell infiltration in the liver, spleen and lungs, and increased survival compared with unmodified C. novyi-NT. Also in the model, Demser increased survival compared with no treatment. In a mouse model of cytokine release induced by an anti-CD3 antibody, Demser decreased plasma levels of cytokines and increased survival. In mouse models of Burkitt lymphoma and B cell acute lymphoblastic leukemia (ALL) with CAR T-induced CRS, Demser or NPPA decreased plasma levels of catecholamines and cytokines. Next steps could include clinical testing of Demser to treat therapy-induced CRS...