期刊
EXPERT OPINION ON INVESTIGATIONAL DRUGS
卷 29, 期 9, 页码 947-959出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/13543784.2020.1793955
关键词
Benznidazole; Chagas disease; clinical trials; drug discovery; fexinidazole; monkeys; nifurtimox; posaconazole; pre-clinical assays; Trypanosoma cruzi
资金
- Departament d'Universitats i Recerca de la Generalitat de Catalunya, Spain [AGAUR] [2017SGR00924]
- Instituto de Salud Carlos III (ISCIII) RICET Network for Cooperative Research in Tropical Diseases [ISCIII] [RD12/0018/0010]
- FEDER
- Spanish Ministry of Science and Innovation-ISCIII project [PI18/01054]
- Ministry of Health, Government of Catalunya [PERIS 20162010 SLT008/18/00132]
- Spanish Ministry of Science and Innovation through the `Centro de Excelencia Severo Ochoa 2019-2023' Program [CEX2018-000806-S]
- Generalitat de Catalunya through the CERCA Program
Introduction Chagas disease treatment relies on the lengthy administration of benznidazole and/or nifurtimox, which have frequent toxicity associated. The disease, caused by the parasiteTrypanosoma cruzi, is mostly diagnosed at its chronic phase when life-threatening symptomatology manifest in approximately 30% of those infected. Considering that both available drugs have variable efficacy by then, and there are over 6 million people infected, there is a pressing need to find safer, more efficacious drugs. Areas covered We provide an updated view of the path to achieve the aforementioned goal. From state-of-the-artin vitroandin vivoassays based on genetically engineered parasites that have allowed high throughput screenings of large chemical collections, to the unfulfilled requirement of having treatment-response biomarkers for the clinical evaluation of drugs. In between, we describe the most promising pre-clinical hits and the landscape of clinical trials with new drugs or new regimens of existing ones. Moreover, the use of monkey models to reduce the pre-clinical to clinical attrition rate is discussed. Expert opinion In addition to the necessary research on new drugs and much awaited biomarkers of treatment efficacy, a key step will be to generalize access to diagnosis and treatment and maximize efforts to impede transmission.
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