In animal model, treating mice with the drug rapamycin protected them against the neurological complications of cerebral malaria.As rapamycin is already approved for use in humans by US Food and Drug Administration, trials in humans for cerebral malaria treatment with this drug may be possible, said the researchers from Harvard T.H. Chan School of Public Health.

Cerebral malaria - a severe form of the disease - is the most serious consequence of infection by the parasite Plasmodium falciparum, resulting in seizures, coma, and death.

"The real importance of this work is the identification of unexpected molecular pathways underlying cerebral malaria that we can now target with existing drugs," said senior author James Mitchell, associate professor of genetics and complex diseases.

The researchers found that leptin - a hormone secreted from fat tissue with roles in suppressing appetite, but also in activating adaptive immune and inflammatory responses - is increased upon infection in a mouse model of cerebral malaria.

This hormone also turns out to be a major bad actor in promoting neurological symptoms and death due to cerebral malaria. Reducing leptin using a variety of means, either genetically, pharmacologically, or nutritionally by reducing food intake during the first two days of infection, protected against cerebral malaria, the findings showed.

The researchers also found that leptin acted primarily on cytotoxic T cells by turning on the well-studied mTOR protein, for which pharmacologic inhibitors are readily available. The study appeared online in the journal Nature Communications.


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