Exploring a new approach for people with Alzheimer’s disease

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

Alzheimer’s disease is an age-related chronic neurodegenerative disease with progressive loss of nerve cells and their connectivity in the brain. Affected patients suffer from memory loss and progressive dementia. Today, over 46 million people live with dementia worldwide and this number is estimated to increase to 131.5 million by 2050. Although current treatments can slightly delay some mental symptoms, there is currently no cure.

It has been known for many years that specialised types of immune cells accumulate around amyloid plaques in patients’ brains (one of the hallmarks of Alzheimer’s disease) and show a dysfunctional activation profile. Recent research has identified the innate immune receptor genes TREM2 and CD33/SIGLEC3 as particularly relevant to Alzheimer’s disease. However, a complete understanding of their exact role and underlying cellular mechanisms is still unclear.

The PHAGO research project aims to fill this knowledge gap and provide tools and assays for targeting these immune receptors to pave the way for the development of drugs that delay the progression of Alzheimer’s disease.

King’s College London will be leading the project’s patient participation efforts, including project and ethical approval and collection of biological samples. King’s will also conduct neuroimaging for the project at the KCL and Guy’s and St Thomas’ PET Centre.

According to Dr Angela Hodges from the National Institute for Health Research (NIHR) Dementia Biomedical Research Unit at King’s College London, who is leading King’s contribution to the project, “This is a very exciting programme of research looking into a new and rapidly-developing area of science in Alzheimer’s Disease. I’m delighted that King’s is involved in the project, and expect the project as a whole to make rapid progress in improving our understanding of this area.”

Dr Andreas Ebneth, project leader at Janssen Pharmaceutica NV, states: “The research project's value is its interdisciplinary approach focused on two relevant immune cell receptors suspected to be involved in Alzheimer’s disease. By bringing together scientific knowledge of leading European experts from different technical areas on TREM2 and CD33, we will be able to establish and exploit innovative tools on TREM2/CD33 suitable for pharmaceutical and industrial application. Over time, our ambition is that these contribute to the development of drugs for the treatment of Alzheimer’s disease.”

Dr Laurent Pradier, project co-leader at Sanofi adds: “I see great potential for this project to develop a way to intervene pharmacologically in the TREM2 and CD33 pathways for the treatment of this devastating disease”.

PHAGO is supported by the IMI with €8.8 million and by further industrial partners with €9.1 million. The project runs over five years and will end on 31st October 2021.

Under the name PHAGO, the new research consortium unites pharmaceutical companies, small biotechnology enterprises and public research organisations from across Europe. Pharmaceutical partners are: Janssen Pharmaceutica NV (Belgium); Sanofi (France); Eli Lilly, AstraZeneca AB (UK); Lundbeck (Denmark); AbbVie (Germany); Roche (Switzerland) and Orion Pharma (Finland). Biotechnology related enterprise members are: Axxam SpA (Italy), Life & Brain GmbH (Germany) and ARTTIC (France). Completing the consortium are academic institutions from across Europe: University Hospital of Bonn, German Center for Neurodegenerative Diseases, Charité – Universitätsmedizin Berlin and Fraunhofer Institute SCAI (Germany); King’s College London, University College London and University of Cambridge (UK); and University of Gothenburg (Sweden).