Novel therapeutic approaches for neglected infectious diseases.

Accelerating R&D for new treatments in NTDs has encountered several fundamental barriers. The complex biology of many of these parasites and their need for vectors for development and transmission challenge the traditional industrial-scale drug discovery programs. The general neglect that these diseases have encountered has meant that basic research findings have not found their way into a drug discovery pipeline. Despite the basic research conducted on the biology of these organisms, the paucity of validated molecular targets and the lack of assays that recapitulate relevant biology of the parasites and are amenable to high-throughput screening (HTS) platforms has hindered the ability to evaluate large sets of compounds with lead-like properties in the pursuit of promising drug discovery starting points.

Although target-based chemotherapeutic screens have been a focus of drug discovery programs in the postgenomic era, there has been a movement toward returning to phenotypic-based whole-organism screening assays.^5,6 Target-based approaches, perhaps with the exception of Trypanosoma brucei, have been hampered by the lack of genetic tools to validate drug targets in these parasites. Thus, running a target-agnostic phenotypic assay upfront in primary screening is a sensible and valid approach to early drug discovery.