Envisioning how Senescent cells may promote Neurodegeneration and trying to counteract this

Envision hypothesizes that scarred cells in the environment can promote neurodegeneration and that targeting these cells may counteract this. This brings together expertise from the UMC Utrecht on the biology of scarred cells (Department of CMM – Center for Molecular Medicine), neurodegeneration (collaborators at Division Brain) and Cleara Biotech B.V. (industry experience with translating anti-scarring compounds).

Neurodegeneration is amongst the most severe types of age-related diseases. The WHO estimates that >55 million people worldwide are living with dementia, with ~10 million new cases per year. Alzhemier’s Disease (AD) contributes for 60-70% to all dementias. Targeting AD has been dubbed the graveyard of drug discovery, with >90% of all trials having failed to deliver. At least in part, this is because much energy has gone into targeting plaques and tangles caused by Aβ and Tau. Alternative solutions are therefore urgently needed.

Whereas the role of the microenvironment is principally acknowledged, much less is clear on how signals thereof might contribute to disease development. WE already obtained preliminary data that scarred cells can impair neuronal biology in vitro and compounds targeting these cells can extend cognitive function in naturally aging mice. Here, we aim to explore whether and how scarred cells may impair neuronal function in advanced 3D neuronal cultures and mice and whether their elimination may also expand cognitive function in models for neurodegeneration, with a focus on AD.

When successful, ENVISIOn will deliver conceptual datasets on which molecular pathways and targetable nodes may promote neurodegeneration (I), proof-of-concept evidence whether targeting these may lead to extende neuronal health and cognitive function (II) and provide a translatable path forward in drug development for compounds that can translate into future clinical trials (III).