Identifying adjunctive therapy in the experimental model of malaria to improve cerebral malaria outcomes

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ABSTRACT Malaria remains a great public health challenge that has resisted worldwide control efforts. Some individuals who are infected with Plasmodium falciparum develop cerebral malaria (CM), which is associated with high morbidity and mortality despite the use of antimalarial therapy. To date, no effective adjunctive therapy is available. As brain swelling was recently identified as the main cause of death in CM, we propose to test dimethyl fumarate (DMF) to modulate neuroinflammation in an experimental cerebral malaria mouse model using histopathological and neuroimaging techniques to define its mechanisms of protection. The preliminary data demonstrate that DMF provides a survival advantage in ECM. Importantly, DMF is FDA-approved for other neuroinflammatory conditions and thus could potentially be repurposed for CM. Our long-term goal is to identify potential adjunctive therapies that reduce brain swelling and increase survival in a pre-clinical model to provide a foundation for future clinical trials and ultimately improve the outcomes of CM.