New Drug Combination for Experimental Late-Stage African Trypanosomiasis: DL-α-Difluoromethylornithine (DFMO) with Suramin

Allen B. Clarkson Jr.Department of Medical and Molecular Parasitology, New York University School of Medicine, New York, New York 10016

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E. Jay BienenDepartment of Medical and Molecular Parasitology, New York University School of Medicine, New York, New York 10016

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Cyrus J. BacchiHaskins Laboratories and Department of Biology, Pace University, New York, New York 10038

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Peter P. McCannMerrell Dow Research Institute, Cincinnati, Ohio 45215

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Henry C. NathanHaskins Laboratories and Department of Biology, Pace University, New York, New York 10038

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Seymour H. HutnerHaskins Laboratories and Department of Biology, Pace University, New York, New York 10038

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Albert SjoerdsmaMerrell Dow Research Institute, Cincinnati, Ohio 45215

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Using a previously described mouse model of late-stage African trypanosomiasis (i.e., involvement of the central nervous system), we demonstrate that a combination of DL-α-difluoromethylornithine (DFMO) and suramin is curative. In the curative protocol, DFMO is given as a 2% solution in the drinking water for 14 days and suramin is administered as a single dose (20 mg/kg intravenously) on day 1 of DFMO administration. Since: 1) DFMO has very low toxicity, 2) suramin is one of the least toxic of the presently used trypanocides, and 3) suramin and DFMO act synergistically in mouse models of both acute and late stage tryanosomiasis, we conclude that this combination offers special promise in the treatment of African trypanosomiasis in man.

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