title: Fexinidazole: a potential new drug candidate for Chagas disease.
abstract: BACKGROUND
  New safe and effective treatments for Chagas disease (CD) are urgently needed. Current chemotherapy options for CD have significant limitations, including failure to uniformly achieve parasitological cure or prevent the chronic phase of CD, and safety and tolerability concerns. Fexinidazole, a 2-subsituted 5-nitroimidazole drug candidate rediscovered following extensive compound mining by the Drugs for Neglected Diseases initiative and currently in Phase I clinical study for the treatment of human African trypanosomiasis, was evaluated in experimental models of acute and chronic CD caused by different strains of Trypanosoma cruzi.
  
  
  RESULTS
  We investigated the in vivo activity of fexinidazole against T. cruzi, using mice as hosts. The T. cruzi strains used in the study were previously characterized in murine models as susceptible (CL strain), partially resistant (Y strain), and resistant (Colombian and VL-10 strains) to the drugs currently in clinical use, benznidazole and nifurtimox. Our results demonstrated that fexinidazole was effective in suppressing parasitemia and preventing death in infected animals for all strains tested. In addition, assessment of definitive parasite clearance (cure) through parasitological, PCR, and serological methods showed cure rates of 80.0% against CL and Y strains, 88.9% against VL-10 strain, and 77.8% against Colombian strain among animals treated during acute phase, and 70% (VL-10 strain) in those treated in chronic phase. Benznidazole had a similar effect against susceptible and partially resistant T. cruzi strains. Fexinidazole treatment was also shown to reduce myocarditis in all animals infected with VL-10 or Colombian resistant T. cruzi strains, although parasite eradication was not achieved in all treated animals at the tested doses.
  
  
  CONCLUSIONS
  Fexinidazole is an effective oral treatment of acute and chronic experimental CD caused by benznidazole-susceptible, partially resistant, and resistant T. cruzi. These findings illustrate the potential of fexinidazole as a drug candidate for the treatment of human CD.
authors.affiliation: Laboratório de Doença de Chagas, Departamento de Ciências Biológicas & Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Campus Universitário, Morro do Cruzeiro, Ouro Preto, Brazil. mtbahia@nupeb.ufop.br
authors.forename: Maria Terezinha
authors.initials: MT
authors.lastname: Bahia
authors.forename: Isabel Mayer
authors.initials: IM
authors.lastname: de Andrade
authors.forename: Tassiane Assíria Fontes
authors.initials: TA
authors.lastname: Martins
authors.forename: Álvaro Fernando da Silva
authors.initials: ÁF
authors.lastname: do Nascimento
authors.forename: Lívia de Figueiredo
authors.initials: Lde F
authors.lastname: Diniz
authors.forename: Ivo Santana
authors.initials: IS
authors.lastname: Caldas
authors.forename: André
authors.initials: A
authors.lastname: Talvani
authors.forename: Bernadette Bourdin
authors.initials: BB
authors.lastname: Trunz
authors.forename: Els
authors.initials: E
authors.lastname: Torreele
authors.forename: Isabela
authors.initials: I
authors.lastname: Ribeiro
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D014355:Chagas Disease / Q000188:drug therapy*; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D009593:Nitroimidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D018512:Parasitemia / Q000188:drug therapy; D016019:Survival Analysis; D016896:Treatment Outcome; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D000981:Antiprotozoal Agents; D009593:Nitroimidazoles; C038307:fexinidazole