Malaria continues to be a major threat to global health.
Artemisinin combination
therapy (ACT) is the recommended treatment for clinical
malaria; however, recent reports of parasite resistance to
artemisinin in certain areas where
malaria is endemic have stressed the need for developing more efficacious ACT. We report that
cysteamine (Cys), the aminothiol used to treat
nephropathic cystinosis in humans, strongly potentiates the efficacy of
artemisinin against the Plasmodium parasite in vivo. Using a mouse model of
infection with Plasmodium chabaudi AS, we observe that Cys dosing used to treat
cystinosis in humans can strongly potentiate (by 3- to 4-fold) the
antimalarial properties of the
artemisinin derivatives
artesunate and
dihydroartemisinin. Addition of Cys to suboptimal doses of
artemisinin delays the appearance of blood
parasitemia, strongly reduces the extent of parasite replication, and significantly improves survival in a model of lethal P. chabaudi
infection. Cys, the
natural product of the
enzyme pantetheinase, has a history of safe use for the clinical management of
cystinosis. Our findings suggest that Cys could be included in novel ACTs to improve efficacy against Plasmodium parasite replication, including
artemisinin-resistant isolates. Future work will include clinical evaluation of novel Cys-containing ACTs and elucidation of the mechanism underlying the potentiation effect of Cys.