Skip to main content

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.

Call for proposal

H2020-JTI-IMI2-2015-05-two-stage
See other projects for this call

Funding Scheme

IMI2-RIA - Research and Innovation action

Coordinator

UNIVERSITATSKLINIKUM BONN
Address
Venusberg-campus 1
53127 Bonn
Germany
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 754 200

Participants (19)

JANSSEN PHARMACEUTICA NV
Belgium
EU contribution
€ 0
Address
Turnhoutseweg 30
2340 Beerse
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
KING'S COLLEGE LONDON
United Kingdom
EU contribution
€ 1 115 000
Address
Strand
WC2R 2LS London
Activity type
Higher or Secondary Education Establishments
DEUTSCHES ZENTRUM FUR NEURODEGENERATIVE ERKRANKUNGEN EV
Germany
EU contribution
€ 1 027 500
Address
Venusberg-campus 1/99
53127 Bonn
Activity type
Research Organisations
CHARITE - UNIVERSITAETSMEDIZIN BERLIN
Germany
EU contribution
€ 538 750
Address
Chariteplatz 1
10117 Berlin
Activity type
Higher or Secondary Education Establishments
UNIVERSITY COLLEGE LONDON
United Kingdom
EU contribution
€ 994 143,75
Address
Gower Street
WC1E 6BT London
Activity type
Higher or Secondary Education Establishments
THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
United Kingdom
EU contribution
€ 1 052 500
Address
Trinity Lane The Old Schools
CB2 1TN Cambridge
Activity type
Higher or Secondary Education Establishments
GOETEBORGS UNIVERSITET
Sweden
EU contribution
€ 372 156,25
Address
Vasaparken
405 30 Goeteborg
Activity type
Higher or Secondary Education Establishments
FRAUNHOFER GESELLSCHAFT ZUR FOERDERUNG DER ANGEWANDTEN FORSCHUNG E.V.
Germany
EU contribution
€ 500 000
Address
Hansastrasse 27C
80686 Munchen
Activity type
Research Organisations
AXXAM SPA
Italy
EU contribution
€ 438 750
Address
Via Meucci 3
20091 Bresso Milano
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
LIFE AND BRAIN GMBH
Germany
EU contribution
€ 451 250
Address
Venusberg-campus 1
53127 Bonn
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
ABBVIE DEUTSCHLAND GMBH & CO KG
Germany
EU contribution
€ 0
Address
Mainzer Str. 81
65205 Wiesbaden
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
ASTRAZENECA AB
Sweden
EU contribution
€ 0
Address
Vastra Maelarhamnen
151 85 Sodertaelje
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Eli Lilly and Company Limited
United Kingdom
EU contribution
€ 0
Address
Lilly House, Priestley Road
RG24 9NL Basingstoke
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
H. LUNDBECK AS
Denmark
EU contribution
€ 0
Address
Ottiliavej 7-9
2500 Valby
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
ORION OYJ

Participation ended

Finland
EU contribution
€ 0
Address
Orionintie 1
02200 Espoo
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
F. HOFFMANN-LA ROCHE AG
Switzerland
EU contribution
€ 0
Address
Grenzacherstrasse 124
4070 Basel
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
SANOFI-AVENTIS RECHERCHE & DEVELOPPEMENT
France
EU contribution
€ 0
Address
Pierre Brossolette 1
91380 Chilly Mazarin
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
ARTTIC
France
EU contribution
€ 593 750
Address
Rue Du Dessous Des Berges 58A
75013 Paris
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
EISAI LIMITED
United Kingdom
EU contribution
€ 0
Address
European Knowledge Centre, Mosquito Way
AL10 9SN Hatfield
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)