Ziel
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 newdrugs 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 at least one new Phase I clinical candidate for each trypanosomatid disease at or shortly after the project completion date.
Wissenschaftliches Gebiet
Programm/Programme
Aufforderung zur Vorschlagseinreichung
FP7-HEALTH-2013-INNOVATION-1
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Finanzierungsplan
CP-FP - Small or medium-scale focused research projectKoordinator
KY16 9AJ St Andrews
Vereinigtes Königreich
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Beteiligte (13)
4200 135 Porto
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94607 OAKLAND CA
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93160 NOISY LE GRAND
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4123 Allschwil
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67400 Illkirch Graffenstaden
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Beteiligung beendet
69120 HEIDELBERG
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75015 PARIS 15
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48160 Derio
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60323 Frankfurt Am Main
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110608 New Delhi
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21040 900 Rio De Janeiro
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75794 Paris
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30620 Bernis
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