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Inflammation and AD: modulating microglia function focussing on TREM2 and CD33 - Sofia ref.: 115976

Objective

Alzheimer’s disease (AD) is an age-related chronic neurodegenerative disease with four main pathological changes in the brain: amyloid plaques, fibrillary tau tangles, inflammation and neuronal loss. Phagocytes around amyloid plaques in late onset AD (LOAD) may be neurotoxic but have limited motility and phagocytic activity, suggesting a dysfunctional activation. These phagocytes express the innate immune receptor TREM2 and CD33. Variants of both genes have been linked to LOAD. The main objectives of PHAGO are to find means of modulating microglia/macrophage activation via TREM2, CD33 and related signalling pathways, and determine the effects of such modulation on microglia/macrophage function, amyloid-β and neurodegeneration, in order to find a treatment for AD. PHAGO will deliver well characterized tools and knowledge through which to manipulate AD risk and provide targets and markers ready to progress to drug development. PHAGO will realise this goal by comprehensively attacking the problem simultaneously at multiple levels, including the molecular structures of the receptors, receptor ligand interactions, ectodomain function in vitro and in vivo, characterisation of receptor processing, modification and signalling, receptor-regulated signalling pathways, gene expression and phagocyte function in cells and animals, comprehensive analysis of receptor knock-in and knock-out models crossed to two different animal models of AD, and identification of receptor-related biomarkers in AD patients. Innovative approaches of PHAGO will include identification of new AD-risk genes using a TREM2 co-expression network approach, brain imaging of AD patients with TREM2 and CD33 variants, and generation of patient iPSC-derived microglia/macrophages to comprehensively phenotype gene variants. The project will also generate tools, such as ligands, reporter cells and optimised assays, suitable for further development of treatments targeting TREM2 and/or CD33 in AD.

Coordinator

UNIVERSITATSKLINIKUM BONN
Net EU contribution
€ 1 754 200,00
Address
Venusberg-campus 1
53127 Bonn
Germany

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Region
Nordrhein-Westfalen Köln Bonn, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00

Participants (20)

JANSSEN PHARMACEUTICA NV
Belgium
Net EU contribution
€ 0,00
Address
Turnhoutseweg 30
2340 Beerse

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Region
Vlaams Gewest Prov. Antwerpen Arr. Turnhout
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Non-EU contribution
€ 2 762 500,00
KING'S COLLEGE LONDON
United Kingdom
Net EU contribution
€ 1 115 000,00
Address
Strand
WC2R 2LS London

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Region
London Inner London — West Westminster
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 50 400,00
DEUTSCHES ZENTRUM FUR NEURODEGENERATIVE ERKRANKUNGEN EV
Germany
Net EU contribution
€ 1 027 500,00
Address
Venusberg-campus 1/99
53127 Bonn

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Region
Nordrhein-Westfalen Köln Bonn, Kreisfreie Stadt
Activity type
Research Organisations
Non-EU contribution
€ 0,00
CHARITE - UNIVERSITAETSMEDIZIN BERLIN
Germany
Net EU contribution
€ 538 750,00
Address
Chariteplatz 1
10117 Berlin

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Region
Berlin Berlin Berlin
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
UNIVERSITY COLLEGE LONDON
United Kingdom
Net EU contribution
€ 994 143,75
Address
Gower Street
WC1E 6BT London

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Region
London Inner London — West Camden and City of London
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
United Kingdom
Net EU contribution
€ 1 052 500,00
Address
Trinity Lane The Old Schools
CB2 1TN Cambridge

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Region
East of England East Anglia Cambridgeshire CC
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
GOETEBORGS UNIVERSITET
Sweden
Net EU contribution
€ 372 156,25
Address
Vasaparken
405 30 Goeteborg

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Region
Södra Sverige Västsverige Västra Götalands län
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
FRAUNHOFER GESELLSCHAFT ZUR FORDERUNG DER ANGEWANDTEN FORSCHUNG EV
Germany
Net EU contribution
€ 500 000,00
Address
Hansastrasse 27c
80686 Munchen

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Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Research Organisations
Non-EU contribution
€ 0,00
AXXAM SPA
Italy
Net EU contribution
€ 438 750,00
Address
Via Meucci 3
20091 Bresso Milano

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SME

The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed.

Yes
Region
Nord-Ovest Lombardia Milano
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Non-EU contribution
€ 0,00
LIFE AND BRAIN GMBH
Germany
Net EU contribution
€ 451 250,00
Address
Venusberg-campus 1
53127 Bonn

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SME

The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed.

Yes
Region
Nordrhein-Westfalen Köln Bonn, Kreisfreie Stadt
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Non-EU contribution
€ 0,00
ABBVIE DEUTSCHLAND GMBH & CO KG
Germany
Net EU contribution
€ 0,00
Address
Mainzer Str. 81
65205 Wiesbaden

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Region
Darmstadt Wiesbaden, Kreisfreie Stadt
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Non-EU contribution
€ 1 277 996,00
ASTRAZENECA AB
Sweden
Net EU contribution
€ 0,00
Address
Vastra Maelarhamnen
151 85 Sodertaelje

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Region
Östra Sverige Stockholm Stockholms län
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Non-EU contribution
€ 378 000,00
ELI LILLY AND COMPANY LTD
United Kingdom
Net EU contribution
€ 0,00
Address
Lilly House Basingview
RG21 4FA Basingstoke

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Region
South East (England) Hampshire and Isle of Wight North Hampshire
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Non-EU contribution
€ 1 137 680,00
H. LUNDBECK AS
Denmark
Net EU contribution
€ 0,00
Address
Ottiliavej 7-9
2500 Valby

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Region
Danmark Hovedstaden Byen København
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Non-EU contribution
€ 1 644 840,00
ORION OYJ

Participation ended

Finland
Net EU contribution
€ 0,00
Address
Orionintie 1
02200 Espoo

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Region
Manner-Suomi Helsinki-Uusimaa Helsinki-Uusimaa
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Non-EU contribution
€ 4 215,46
F. HOFFMANN-LA ROCHE AG
Switzerland
Net EU contribution
€ 0,00
Address
Grenzacherstrasse 124
4070 Basel

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Region
Schweiz/Suisse/Svizzera Nordwestschweiz Basel-Stadt
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Non-EU contribution
€ 480 000,00
SANOFI-AVENTIS RECHERCHE & DEVELOPPEMENT
France
Net EU contribution
€ 0,00
Address
Pierre Brossolette 1
91380 Chilly Mazarin

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Region
Ile-de-France Ile-de-France Essonne
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Non-EU contribution
€ 1 500 000,00
ARTTIC
France
Net EU contribution
€ 583 750,00
Address
39 Rue Des Mathurins
75008 Paris

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Region
Ile-de-France Ile-de-France Paris
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Non-EU contribution
€ 0,00
Third-party

Legal entity other than a subcontractor which is affiliated or legally linked to a participant. The entity carries out work under the conditions laid down in the Grant Agreement, supplies goods or provides services for the action, but did not sign the Grant Agreement. A third party abides by the rules applicable to its related participant under the Grant Agreement with regard to eligibility of costs and control of expenditure.

ARTTIC INNOVATION GMBH
Germany
Net EU contribution
€ 10 000,00
Address
Oskar-von-miller-ring 29
80333 Munchen

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Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Non-EU contribution
€ 0,00
EISAI LIMITED
United Kingdom
Net EU contribution
€ 0,00
Address
European Knowledge Centre, Mosquito Way
AL10 9SN Hatfield

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Region
East of England Bedfordshire and Hertfordshire Hertfordshire
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Non-EU contribution
€ 147 600,00