University of Oxford Momentum Award – Dementias

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Research and drug discovery for Alzheimer’s disease (AD) is undergoing a minor crisis with a
paucity of novel therapeutic approaches that is human evidence-based. Whilst, human genetic
studies have identified AD associated variants important for CNS glial function, there is
uncertainty over whether inflammation plays a beneficial or deleterious role. As a result, many
pharma companies are hesitant before committing significant resources to this novel therapeutic
opportunity. Our proposal is therefore focused on the scientific theme “Microglial interactions in
Alzheimer’s Disease”. The indicative projects will leverage four key capabilities within the
University of Oxford that represent untapped potential and are ripe for development for dementia
research, (1) access to human primary CNS cell types from human tissue coupled with single
cell analysis, (2) Human iPSC derived microglia, (3) High order imaging analysis of cellular
phenotypes driven by machine learning, (4) Protein-protein interaction disruption to probe
signalling pathways. The proposed projects approaches neuro-inflammation in AD through these
technical capabilities and are supported by world-leading bioinformatics and unrivalled structural
genomics consortium (SGC) pharmacological tools. These tools enable pharmacological pilot
studies within the projects, which if successful, will more rapidly lead to drug discovery projects
because of the enabling structural knowledge and chemical starting points held within the SGC.
Momentum funds will support the recruitment of a new research leader from outside the UK, as
well as supporting early career high flyers within Oxford. Our pharma partners and institution
leverages the MRC funds with significant institutional funds, platforms, space and expertise
totalling ~£2million (~£850K from the institution and $1.5million industry in-kind). We have
developed strong partnerships with Oxford University Hospital NHS Trust and industry including
world-leaders in single cell biology and dementia drug discovery. The Award will support the
diversification of target identification and develop human in vitro models that are more likely to
be predictive of clinical outcomes compared to current dominant murine models. Our approach
will facilitate synergy between disciplines and maximise the contribution of the grant towards the
acceleration of new dementia research in Oxford.