Abstract:
With half of the world's population at risk for malaria infection and with drug resistance on
the rise, the search for mutation-resistant therapies has intensified. We report here a therapy
for Plasmodium falciparum malaria that acts by inhibiting the phosphorylation of erythrocyte
membrane band 3 by an erythrocyte tyrosine kinase. Because tyrosine
phosphorylation of band 3 causes a destabilization of the erythrocyte membrane required
for parasite egress, inhibition of the erythrocyte tyrosine kinase leads to parasite entrapment
and termination of the infection. Moreover, because one of the kinase inhibitors to
demonstrate antimalarial activity is imatinib, i.e. an FDA-approved drug authorized for use
in children, translation of the therapy into the clinic will be facilitated. At a time when drug
resistant strains of P. falciparum are emerging, a strategy that targets a host enzyme that
cannot be mutated by the parasite should constitute a therapeutic mechanism that will
retard evolution of resistance.
