New approach to help patients suffering from Alzheimer’s disease

On 1^st November 2016 the Innovative Medicines Initiative (IMI) together with an association of industrial partners launched PHAGO, an innovative research project devoted to the development of immunomodulatory therapies for Alzheimer’s disease (AD).

Objectives

Our main Project Objective is to understand the function of TREM2, CD33 and related pathways in AD, so that they might be targeted to treat the disease in future. We have created this public-private partnership of leading European experts on TREM2 and CD33

1. to bring together scientific knowledge from different technical fields on TREM2 and CD33.
2. to allow rapid transfer of novel academic scientific findings on TREM2 and CD33 and related targets towards pharmaceutical and industrial research use.
3. to acquire key knowledge on the role of TREM2/CD33 in AD, including the development of validated assays, and identification of tool compounds and/or tool antibodies targeted to TREM2/CD33 and related target functions.
4. to generate innovative tools for investigating TREM2/CD33 and related pathways that are suitable for pharmaceutical and industrial research use.
5. to generate new knowledge regarding TREM2/CD33 and neuroinflammation to increase the competitiveness of European SMEs and pharmaceutical companies.
6. to disseminate and enable exploitation of this knowledge to relevant stakeholders for further development, including by the creation of a knowledge database containing data generated in this action.

Approach

The overall goal is to identify druggable points for intervention in the TREM2 and CD33-signalling pathways to modulate microglial or macrophage function for future development of treatment options for Alzheimer’s disease.  We aim to systematically use the models and tools developed by our interdisciplinary consortium to unite molecular, cellular, biochemical, bioinformatics and clinical expertise, e.g.:

• Genetics, bioinformatics and systems biology
• positron emission tomography (PET)-imaging of AD patients
• microglial biomarkers
• induced pluripotent stem cell (iPSC) technologies
• cellular screening assays
• advanced knowledge databases

Impact
The ambition is to improve patient outcomes through a better understanding of the biology of TREM2 and CD33 and their biological networks and pathways, and pave the way for future development of therapies aimed at phagocyte dysfunction in AD. We expect to achieve this goal by means of modulating microglia/macrophage activation through TREM2, CD33 and related signalling pathways, and determine the effects of such modulation on microglia/macrophage function. Thus, European research and pharmaceutical industries will benefit from understanding fundamental AD disease processes and from identification of druggable points in the TREM2/CD33 signalling pathway to regulate the phagocytes. On a long-term perspective we also hope to achieve benefits for patients with AD or related neurodegenerative diseases.

The parties involved
To fulfill our objectives, we bring together leading European experts with complementing expertise on TREM2 and CD33. The new research consortium unites 8 pharmaceutical companies, 3 small biotechnology enterprises and 8 public research organisations from 9 countries across Europe, under the leadership of Janssen Pharmaceutica NV (Belgium) and the University Hospital of Bonn (Germany), with the common vision and goal to understand the function of CD33 and TREM2 receptors in Alzheimer’s disease. Our ultimate aim is to bring forward a therapy for this disease that is based on immunomodulatory approaches.

Funding
PHAGO is supported by the IMI_JU with a financial contribution of 8.8 million Euros, which will be complemented by an in-kind contribution of 9.1 million Euros provided by the industrial partners. The project runs over five years until 31^st October 2021.