title: Current and Future Chemotherapy for Chagas Disease.
abstract: Human American trypanosomiasis, commonly called Chagas disease, is one of the most neglected illnesses in the world and remains one of the most prevalent chronic infectious diseases of Latin America with thousands of new cases every year. The only treatments available have been introduced five decades ago. They have serious, undesirable side effects and disputed benefits in the chronic stage of the disease - a characteristic and debilitating cardiomyopathy and/or megavisceras. Several laboratories have therefore focused their efforts in finding better drugs. Although recent years have brought new clinical trials, these are few and lack diversity in terms of drug mechanism of action, thus resulting in a weak drug discovery pipeline. This fragility has been recently exposed by the failure of two candidates; posaconazole and E1224, to sterilely cure patients in phase 2 clinical trials. Such setbacks highlight the need for continuous, novel and high quality drug discovery and development efforts to discover better and safer treatments. In this article we will review past and current findings on drug discovery for Trypanosoma cruzi made by academic research groups, industry and other research organizations over the last half century. We also analyze the current research landscape that is now better placed than ever to deliver alternative treatments for Chagas disease in the near future.
authors.forename: Luís
authors.initials: L
authors.lastname: Gaspar
authors.forename: Carolina B
authors.initials: CB
authors.lastname: Moraes
authors.forename: Lucio H
authors.initials: LH
authors.lastname: Freitas-Junior
authors.forename: Stefania
authors.initials: S
authors.lastname: Ferrari
authors.forename: Luca
authors.initials: L
authors.lastname: Costantino
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Costi
authors.forename: Ross P
authors.initials: RP
authors.lastname: Coron
authors.forename: Terry K
authors.initials: TK
authors.lastname: Smith
authors.forename: Jair L
authors.initials: JL
authors.lastname: Siqueira-Neto
authors.forename: James H
authors.initials: JH
authors.lastname: McKerrow
authors.affiliation: Instituto de Investigacao e Inovacao em Saude, Rua Alfredo Allen 208, 4200-135 Porto, Portugal. cordeiro@ibmc.up.pt.
authors.forename: Anabela
authors.initials: A
authors.lastname: Cordeiro-da-Silva
mesh_terms: D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D014355:Chagas Disease / Q000188:drug therapy*; D055808:Drug Discovery / Q000639:trends*; D006801:Humans; D014349:Trypanosoma cruzi / Q000502:physiology
chemical_list: D000981:Antiprotozoal Agents