Funding outcome

Malaria is a major cause of death in children globally. It mostly affects young children in sub-Saharan Africa, who are at risk of severe disease, death, and mental disability following infection. Cerebral malaria is a deadly complication which occurs when the brain is involved. Despite the world's best antimalarial drugs, the mortality rate is still about 20%, meaning that one in five children with cerebral malaria will die of their infection. Furthermore, 25% (one in four) children who survive cerebral malaria will be left with lasting brain problems. New treatment strategies are needed to reduce the number of deaths as well as the long term effects of cerebral malaria on the brain. We think that some new anti-cancer drugs can be used for an entirely different purpose: to protect the brain in cerebral malaria. This surprising re-purposing of recently licenced medications makes sense because these dugs target a molecule called VEGFR2 which causes leaky vessels and brain swelling. By blocking this molecule, we think that we can improve outcomes in cerebral malaria. We want to test these drugs in 2 ways: a model of the blood brain barrier using cells in a 'petri dish,' and an animal model of disease. We will test these drugs to see if they can protect the brain by stabilizing the 'blood-brain barrie~• which separates the brain cells from the bloodstream. If we find promising molecules, this will be significant for several reasons: (1) it will show that the VEGFR2 pathway is a good target for malaria treatment; and (2) it will suggest new treatments that could be tried in clinical trials of children with cerebral malaria.