Blocking inhibitor of apoptosis proteins in liver cells to treat malaria

INDICATION: Malaria

Targeting IAP, a family of apoptosis-blocking proteins that includes BIRC2 and BIRC3, could treat malaria by clearing liver infection. In mice infected with Plasmodium berghei sporozoites, the parasite stage that infects liver cells, hepatocyte-specific BIRC2 knockout plus systemic BIRC3 knockout lowered liver parasite load and increased survival. In the sporozoite-infected mice and in mice with mosquito-transmitted disease, the IAP antagonist birinapant reduced liver parasite burden, delayed and attenuated blood-stage parasitemia and improved survival. Birinapant treatment of primary infections also induced adaptive immunity to the parasite and led to lower liver levels of the parasite following sporozoite rechallenge. In the sporozoite infection model, another IAP antagonist, LCL161, also decreased liver parasite burden...