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Development of a pre-clinical blood test for prion diseases

Project information

Grant agreement ID: 19090

  • Start date

    1 June 2006

  • End date

    31 May 2009

Funded under:

FP6-LIFESCIHEALTH

  • Overall budget:

    € 2 493 500

  • EU contribution

    € 2 450 000

Coordinated by:

HET NEDERLANDS KANKER INSTITUUT

Netherlands

Objective

There are currently no tests for early prion diagnosis. Such tests would help to prevent transmission through blood, biologicals, the food chain, and medical procedures, and (ii)identify candidates for emerging anti-prion therapies and prophylactic procedures, especially among silent carriers of pathogenic PrP mutations. Current tests are based on the identification of PrPSc or of characteristic pathologies in brain samples collected post mortem. Recent advances have shown that minute amounts of PrPSc exist in body fluids such as blood. Although these PrPSc levels are too low to be detected reliably by existing methods, they point to the feasibility of using these fluids whith improved methods. We propose to develop methodologies for the pre-clinical detection of prions in body fluids, based on (i) PrPSc, and (ii) novel surrogate (non-PrP) markers of prion diseases. To this end, we have assembled a powerful consortium of partners with proven clinical, experimental and industrial achievements. PrPSc detection in body fluids will be achieved by systematically improving every step in the process. (i) Sample fractionation: Fluids will be fractionated to identify fractions enriched in PrPSc. For example, FACS-based fractionation of white blood cells (WBC) will identify PrPSc containing cells and organelles. (ii) PrPSc concentration: novel PrPSc-binding molecules will be developed and used to capture and concentrate PrPSc prior to detection. (iii) PrPSc amplification: We will develop in vitro and cell culture-based approaches to amplify PrPSc in WBC prior to its detection. (iv) PrPSc detection: We will use improved PrP antibodies and use methods to detect both protease-resistant and protease-sensitive PrPSc. Surrogate markers and molecular 'signatures' of prion diseases will be identified using novel highly sensitive proteomic and genomic approaches such as SELDI and DNA microarrays. Proprietary software will be developed for analysis.

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Coordinator

HET NEDERLANDS KANKER INSTITUUT

Address

Plesmanlaan 121
Amsterdam

Netherlands

Participants (12)

THE HEBREW UNIVERSITY OF JERUSALEM

Israel

KAROLINSKA INSTITUTET

Sweden

UNIVERSIDADE DE SANTIAGO DE COMPOSTELA

Spain

UNIVERSITY OF EDINBURGH

United Kingdom

UNIVERSITY OF ULM, MEDICAL FACULTY

Germany

SLOVENSKA ZDRAVOTNICKA UNIVERZITA

Slovakia

INSTITUT PASTEUR

France

ROBERT-KOCH-INSTITUT

Germany

FRIEDRICH-LOEFFLER-INSTITUT, FEDERAL INSTITUTE FOR ANIMAL HEALTH

Germany

MATRIX ADVANCED SOLUTIONS GERMANY GMBH

Germany

STICHTING SANQUIN BLOEDVOORZIENING

Netherlands

HEINRICH HEINE UNIVERSITÄT DÜSSELDORF

Germany

Project information

Grant agreement ID: 19090

  • Start date

    1 June 2006

  • End date

    31 May 2009

Funded under:

FP6-LIFESCIHEALTH

  • Overall budget:

    € 2 493 500

  • EU contribution

    € 2 450 000

Coordinated by:

HET NEDERLANDS KANKER INSTITUUT

Netherlands