TLR9 Inhibitor for Cerebral Malaria
Eisai Co., Ltd.'s ER-820446 is a selective inhibitor of Toll Like Receptor 9 (TLR9) signaling. TLRs are mediators of innate immunity. In vitro, ER-820446 inhibits CpG oligonucleotide (TLR9 agonist)-mediated induction of transcription factors in TLR9 transfected cells and the production of proinflammatory cytokines in dendritic cells. In a short term in vivo model in mice, administration of ER-820446 prevented a systemic cytokine response to a s.c. challenge with CpG oligonucleotide. In a Plasmodium chabaudi malaria murine infection model, ER-820446 did not reduce parasitemia, but prevented spontaneous release of proinflammatory cytokines triggered in response to infection in vivo. In a Plasmodium berghei cerebral malaria murine model, prophylactic treatment with ER-820446 significantly reduced mortality due to cerebral malaria. Pre-clinical development activities have been initiated for ER-820446, in conjunction with researchers at the Oswaldo Cruz Foundation in Brazil and the University of Massachusetts in the USA.