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

Allen B. Clarkson, Jr., E. Jay Bienen, Cyrus J. Bacchi, Peter P. McCann, Henry C. Nathan, Seymour H. Hutner AND Albert Sjoerdsma

Department of Medical and Molecular Parasitology, New York University School of Medicine, New York, New York 10016
Haskins Laboratories and Department of Biology, Pace University, New York, New York 10038
Merrell Dow Research Institute, Cincinnati, Ohio 45215

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--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.

Accepted for publication May 4, 1984.

^* The authors wish to thank Dr. Michael Marmor of New York University School of Medicine for providing a statistical analysis of the data. This work was supported in part by grants from the National Institute of Allergy and Infectious Diseases, N.I.H. (AI-17340) and from the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (780194).

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