Periodic Reporting for period 5 - PHAGO (Inflammation and AD: modulating microglia function focussing on TREM2 and CD33 - Sofia ref.: 115976)
Periodo di rendicontazione: 2020-11-01 al 2022-04-30
Phagocytic cells, namely microglia, accumulate around amyloid plaques in the brains of AD patients and show a dysfunctional activation profile. Recent systems biology approaches have identified two innate immune receptor genes TREM2 and CD33/SIGLEC3 as disease relevant players in AD. TREM2 and CD33/SIGLEC3 might be attractive targets for development of treatments, but knowledge on their mechanistic contribution to AD has been poor at the beginning of the PHAGO project.
PHAGO filled this knowledge gap and provided tools and assays for targeting these both innate immune receptors, namely TREM2 and CD33/SIGLEC3. PHAGO enabled rapid transfer of the academic scientific findings on TREM2 and CD33 towards the collaborating pharmaceutical industries. PHAGO disseminated the generated knowledge regarding TREM2/CD33 to relevant stakeholders for further development by presentations and peer-reviewed publications. PHAGO also created a knowledge database containing data generated by PHAGO in addition to publicly available data resources. PHAGO exploited intellectual property related to inventions on TREM2-cleavage and an improved protocol for up-scaled production of microglia-like/-precursor cells and macrophage cell using mesh macrocarriers by filing patent applications.
PHAGO achieved these goals by bringing together experts from industry and academia in a powerful collaboration. In addition, PHAGO reached out to other IMI-collaborative undertakings in order to maximally utilize synergisms throughout the European Research landscape.
Thus, PHAGO paved the way for the future development of drugs that potentially might delay the progression of Alzheimer’s disease by targeting TREM2 or CD33/SIGLEC3.
PHAGO partners filed two patent applications. Firstly, DZNE (Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. Munich, Germany) showed that antibodies against the stalk region of TREM2 can enhance the protective clearance function of microglia and might have possible future potential for a clinical application. Secondly, Life & Brain GmbH (Bonn, Germany) established an up-scalable technique for production of microglia-like/-precursor cells and macrophage cell using mesh macrocarriers.
To achieve this output, PHAGO had regularly project discussion through reports, teleconferences within and between work packages and remote meetings via videoconferences. In total, six General Assembly Meetings have been organized to discuss the status of the project within the whole consortium.