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Summary

The trypanosomatid diseases, leishmaniasis, Human African trypanosomiasis (HAT) and  Chagas disease (CD), continue to impart a heavy toll on human health. The treatments  available are limited and threatened by drug resistance with few new drugs in the pipeline.  The KINDReD consortium integrates five leading academic laboratories in Europe (Portugal,  United Kingdom, and Switzerland), the USA (California) and South America (Brazil) with high  throughput screening (HTS) facilities equally distributed between all three major kinetoplastid  parasites. Intracellular amastigote screening will be employed as the most  relevant for Leishmania spp and T cruzi. Compound libraries (focused,  diversity oriented or natural) will be screened in these systems, as well  as compound series devised through target screening and in silico  approaches. For carefully chosen protein targets, all three kinetoplastid  parasite homologs will be screened against the closest human homolog  to establish selectivity. Promising lead compounds will be optimised for  efficacy and tolerability in cell-based and animal disease models.  Toxicological markers will be evaluated in human cell lines prior to  toxicity (acute,subacute,chronic) testing in lower then higher mammals.  In parallel, and in line with the FDA's ‘Critical Path Initiative’, several  check point controls will be built into the pipeline to flag, identify and allow early correction of  potential toxicity/efficacy issues. These will include (i) a systems biology approach to identify  drug target and off-target interactions via activity-based chemoproteomics (ii) ‘uptake and  metabolism’as potential modulators of drug efficacy and/or resistance and (iii) the  establishment of a firm set of rules for drug efficacy and safety in kinetoplastid chemotherapy.  Our goal is to strengthen the drug development pipeline in order to achieve one new Phase I  clinical candidate for each trypanosomatid disease at or shortly after the project completion  date.

Scientific programme

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© IP Research Consulting 2014
Drug Development Summary