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Kinetoplastid Drug Development: strengthening the preclinical pipeline

Kinetoplastid Drug Development: strengthening the preclinical pipeline

Objective

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.

Coordinator

THE UNIVERSITY COURT OF THE UNIVERSITY OF ST ANDREWS

Address

North Street 66 College Gate
Ky16 9aj St Andrews

United Kingdom

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 598 489,46

Administrative Contact

Trish Starrs (Ms.)

Participants (13)

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INSTITUTO DE BIOLOGIA MOLECULAR E CELULAR-IBMC

Portugal

EU Contribution

€ 539 999,20

THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

United States

EU Contribution

€ 491 800

IP RESEARCH CONSULTING SASU

France

EU Contribution

€ 653 718,48

SCHWEIZERISCHES TROPEN- UND PUBLIC HEALTH-INSTITUT

Switzerland

EU Contribution

€ 347 712

NovAliX

France

EU Contribution

€ 992 400

GRAFFINITY PHARMACEUTICALS GMBH

Germany

EU Contribution

€ 124 200,06

COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES

France

EU Contribution

€ 359 609,25

Innovative Technologies in Biological Systems

Spain

EU Contribution

€ 413 064

JOHANN WOLFGANG GOETHE-UNIVERSITATFRANKFURT AM MAIN

Germany

EU Contribution

€ 308 750

THE ALL-INDIA INSTITUTE OF MEDICAL SCIENCES

India

EU Contribution

€ 244 054

FUNDACAO OSWALDO CRUZ

Brazil

EU Contribution

€ 247 204,80

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS

France

EU Contribution

€ 365 400

PHYLOGENE

France

EU Contribution

€ 313 590

Project information

Grant agreement ID: 602773

Status

Closed project

  • Start date

    1 September 2013

  • End date

    31 August 2016

Funded under:

FP7-HEALTH

  • Overall budget:

    € 7 915 469,55

  • EU contribution

    € 5 999 991,25

Coordinated by:

THE UNIVERSITY COURT OF THE UNIVERSITY OF ST ANDREWS

United Kingdom