PHAGO

Inflammation and AD: modulating microglia function - focussing on TREM2 and CD33
PHAGO logo

FACTS & FIGURES

Start Date
End Date
Call
IMI2 - Call 5
Grant agreement number
115976

Type of Action: 
RIA (Research and Innovation Action)

Contributions
IMI Funding
8 838 000
EFPIA in kind
9 240 096
Other
10 080
Total Cost
18 088 176

Summary

Clumps of proteins in the brain called amyloid plaques are a hallmark of Alzheimer’s disease, and very often specialised immune cells cluster around these plaques. Recent research has shown that two genes involved in the immune system, TREM2 and CD33, appear to be involved in this immune response to Alzheimer’s disease and could therefore be targets for drugs. However, their exact role in the disease is still poorly understood. The PHAGO project aims to develop tools and methods to study the workings of these genes. The project results will therefore pave the way for the development of novel drugs that could tackle Alzheimer’s disease via this route.

Achievements & News

PHAGO reveals complex role of TREM2 gene in Alzheimer’s disease
January 2019

Scientists have shed new light on how a gene called TREM2 influences the progression of Alzheimer’s disease in different ways in the early and later stages. The findings, published in Nature Neuroscience, add to our understanding of the disease and have major implications for drug development. ###The work was funded in part by IMI through the PHAGO project. TREM2 codes for the TREM2 protein, which activates immune cells in the brain called microglia. Microglia play a vital role in the removal of amyloid plaques, the tangled toxic proteins which are a hallmark of Alzheimer’s disease. In this study, the researchers showed that in mice with early signs of plaque deposition (and a functioning TREM2 gene), microglia cluster around small plaques and cause them to disintegrate. In mice lacking a functional TREM2 gene, the microglia were not able to break up the amyloid plaques. This suggests that in early stage Alzheimer’s disease, activating TREM2 could help to prevent the build-up of toxic amyloid plaques.

However, the results of a similar test in mice with more advanced plaque deposition paint a different picture. There, the amyloid plaques grew faster in mice with a functioning TREM2 gene than in mice without it. Further analyses showed that in the microglia, TREM2 also stimulates the production of a protein called ApoE, which is by far the strongest genetic risk factor for developing sporadic Alzheimer’s disease, and is thought to promote the aggregation of amyloid plaques. ‘Our findings indicate that future therapies will need to be applied in a stage-specific manner,’ says Christian Haass of DZNE Munich and Ludwig-Maximilians University, who led the research. ‘Based on the outcome of our study, activation of microglia by TREM2 would be a useful strategy to apply during the early phase of the condition.’ Professor Haass and his colleagues are now working on antibodies that could stabilise the TREM2 protein, increasing its ability to activate microglia.

Participants Show participants on map

EFPIA companies
  • Abbvie Deutschland GMBH & Co Kg, Wiesbaden, Germany
  • Astrazeneca AB, Södertälje, Sweden
  • Eisai Limited, Hatfield, United Kingdom
  • Eli Lilly and Company Limited, Basingstoke, United Kingdom
  • F. Hoffmann-La Roche AG, Basel, Switzerland
  • H. Lundbeck As, Valby, Denmark
  • Janssen Pharmaceutica Nv, Beerse, Belgium
  • Orion Oyj, Espoo, Finland
  • Sanofi-Aventis Recherche & Developpement, Chilly Mazarin, France
Universities, research organisations, public bodies, non-profit groups
  • Charite - Universitaetsmedizin Berlin, Berlin, Germany
  • Deutsches Zentrum Fur Neurodegenerative Erkrankungen Ev, Bonn, Germany
  • Fraunhofer Gesellschaft Zur Foerderung Der Angewandten Forschung E.V., München, Germany
  • Goeteborgs Universitet, Gothenburg, Sweden
  • King'S College London, London, United Kingdom
  • Universitatsklinikum Bonn, Bonn, Germany
  • University College London, London, United Kingdom
  • University of Cambridge, Cambridge, United Kingdom
Small and medium-sized enterprises (SMEs) and mid-sized companies (<€500 m turnover)
  • Arttic, Paris, France
  • Axxam S.A, Bresso (Milan), Italy
  • Life And Brain GMBH, Bonn, Germany

CONTACT

Project leader
Dr. Andreas Ebneth
Janssen Pharmaceutica NV
AEBNETH[at]its.jnj.com
Project coordinator
Beate BECKER
UNIVERSITATSKLINIKUM BONN
Beate.Becker[at]ukb.uni-bonn.de
E-mail address
info[at]phago.eu