Effective drug discovery in Chagas disease.

Animals, including humans, with chronic Trypanosoma cruzi infection can be successfully treated and cured using existing FDA-approved drugs and newly discovered compounds. T. cruzi and Chagas disease offer unequalled model systems and highly accessible host species for efficient drug discovery and for determining drug efficacy. New understanding of T. cruzi biology and infection characteristics identify potential new directions, assays, and approaches for streamlining drug discovery for T. cruzi. Currently licensed compounds can be more effectively dosed to achieve a higher frequency of parasitological cures. There appears to be limited risk of development and spread of drug resistance in T. cruzi using currently available and highly effective 'in-development' compounds. The Chagas field has gone >50 years without tangible progress toward new therapies. My colleagues and I have recently reported on a benzoxaborole compound that achieves consistent parasitological cure in experimentally infected mice and in naturally infected non-human primates (NHPs). While these results do not assure success in human clinical trials, they significantly de-risk this process and form a strong justification for such trials. Highly effective drug discovery depends on a solid understanding of host and parasite biology and excellent knowledge in designing and validating chemical entities. This opinion piece seeks to provide perspectives on the process that led to the discovery of AN15368, with the hope that this will facilitate the discovery of additional clinical candidates for Chagas disease. [ABSTRACT FROM AUTHOR]