Imatinib augments standard malaria combination therapy without added toxicity.

Autor:	Chien HD; College of Health Science, Vin University, Hanoi, Vietnam., Pantaleo A; Department of Biomedical Sciences, University of Sassari, Sassari, Italy., Kesely KR; Department of Chemistry, Purdue University, West Lafayette, IN., Noomuna P; Department of Chemistry, Purdue University, West Lafayette, IN., Putt KS; Institute for Drug Discovery, Purdue University, West Lafayette, IN., Tuan TA; Huong Hoa District Health Center, Quang Tri, Vietnam., Low PS; Department of Chemistry, Purdue University, West Lafayette, IN.; Institute for Drug Discovery, Purdue University, West Lafayette, IN., Turrini FM; Department of Oncology, University of Turin, Turin, Italy.
Jazyk:	angličtina
Zdroj:	The Journal of experimental medicine [J Exp Med] 2021 Oct 04; Vol. 218 (10). Date of Electronic Publication: 2021 Aug 26.
DOI:	10.1084/jem.20210724
Abstrakt:	To egress from its erythrocyte host, the malaria parasite, Plasmodium falciparum, must destabilize the erythrocyte membrane by activating an erythrocyte tyrosine kinase. Because imatinib inhibits erythrocyte tyrosine kinases and because imatinib has a good safety profile, we elected to determine whether coadministration of imatinib with standard of care (SOC) might be both well tolerated and therapeutically efficacious in malaria patients. Patients with uncomplicated P. falciparum malaria from a region in Vietnam where one third of patients experience delayed parasite clearance (DPC; continued parasitemia after 3 d of therapy) were treated for 3 d with either the region's SOC (40 mg dihydroartemisinin + 320 mg piperaquine/d) or imatinib (400 mg/d) + SOC. Imatinib + SOC-treated participants exhibited no increase in number or severity of adverse events, a significantly accelerated decline in parasite density and pyrexia, and no DPC. Surprisingly, these improvements were most pronounced in patients with the highest parasite density, where serious complications and death are most frequent. Imatinib therefore appears to improve SOC therapy, with no obvious drug-related toxicities. Competing Interests: Disclosures: K.S. Putt reported "other" from Erythrocure, Inc. outside the submitted work. K.S. Putt, P.S. Low, and F.M. Turrini are members of the Board of Directors for Erythrocure, Inc. P.S. Low reported a patent to the US Patent Office pending. No other disclosures were reported. (© 2021 Chien et al.)
Databáze:	MEDLINE
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