Cysteamine, the molecule used to treat cystinosis, potentiates the antimalarial efficacy of artemisinin.

Abstract

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.

• Authors: Gundula Min-Oo, Anny Fortin, Jean-François Poulin, Philippe Gros
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 54 Issue 8 Pg. 3262-70 (Aug 2010) ISSN: 1098-6596 [Electronic] United States
• PMID: 20479197 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimalarials
• Artemisinins
• Cysteamine

Topics

• Animals
• Antimalarials (administration & dosage, therapeutic use)
• Artemisinins (administration & dosage, therapeutic use)
• Cysteamine (administration & dosage, pharmacokinetics, therapeutic use)
• Cystinosis (drug therapy)
• Dose-Response Relationship, Drug
• Drug Resistance
• Drug Synergism
• Drug Therapy, Combination
• Humans
• Malaria (drug therapy, mortality, parasitology)
• Mice
• Mice, Inbred C57BL
• Plasmodium chabaudi (drug effects, growth & development)