Bernhard, S. and Kaiser, M. and Burri, C. and Mäser, P.. (2022) Fexinidazole for human African trypanosomiasis, the fruit of a successful public-private partnership. Diseases, 10 (4). p. 90.
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Official URL: https://edoc.unibas.ch/90385/
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Abstract
After 100 years of chemotherapy with impractical and toxic drugs, an oral cure for human African trypanosomiasis (HAT) is available: Fexinidazole. In this case, we review the history of drug discovery for HAT with special emphasis on the discovery, pre-clinical development, and operational challenges of the clinical trials of fexinidazole. The screening of the Drugs for Neglected Diseases initiative (DNDi) HAT-library by the Swiss TPH had singled out fexinidazole, originally developed by Hoechst (now Sanofi), as the most promising of a series of over 800 nitroimidazoles and related molecules. In cell culture, fexinidazole has an IC50 of around 1 microM against Trypanosoma brucei and is more than 100-fold less toxic to mammalian cells. In the mouse model, fexinidazole cures both the first, haemolymphatic, and the second, meningoencephalitic stage of the infection, the latter at 100 mg/kg twice daily for 5 days. In patients, the clinical trials managed by DNDi and supported by Swiss TPH mainly conducted in the Democratic Republic of the Congo demonstrated that oral fexinidazole is safe and effective for use against first- and early second-stage sleeping sickness. Based on the positive opinion issued by the European Medicines Agency in 2018, the WHO has released new interim guidelines for the treatment of HAT including fexinidazole as the new therapy for first-stage and non-severe second-stage sleeping sickness caused by Trypanosoma brucei gambiense (gHAT). This greatly facilitates the diagnosis and treatment algorithm for gHAT, increasing the attainable coverage and paving the way towards the envisaged goal of zero transmission by 2030.
Faculties and Departments: | 09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) 09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Parasite Chemotherapy (Mäser) 09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medicine (MED) > Medicines Implementation Research (Burri) |
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UniBasel Contributors: | Bernhard, Sonja and Kaiser, Marcel and Burri, Christian and Mäser, Pascal |
Item Type: | Article, refereed |
Article Subtype: | Research Article |
ISSN: | 2079-9721 (Print)2079-9721 (Linking) |
Note: | Publication type according to Uni Basel Research Database: Journal article |
Language: | English |
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Last Modified: | 21 Dec 2022 16:55 |
Deposited On: | 21 Dec 2022 16:55 |
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