Neurology Central

Dementia-on-a-chip: Trevor Bushell and Michele Zagnoni on microfluidics, collaboration and the future of dementia research

The use of on-a-chip technologies has seen enormous growth across the biomedical sciences in recent years, but how can this approach be harnessed to further understand dementia and its contributing diseases, and develop new therapies? We spoke to Trevor Bushell and Michele Zagnoni (both University of Strathclyde, UK) about how they’ve brought together their respective expertise in neuroscience and bioengineering to develop “dementia-on-a-chip” microfluidic technologies. In this interview, they discuss their joint projects, including how they’re enabling predictions on the efficacy and pharmacological effects of agents targeting tau in Alzheimer’s disease; the importance of collaboration; and their forecast for the future of dementia research.

Can you talk us through your current collaborative projects?

Michele and I are currently collaborating on a number of projects funded by the NC3Rs (National Centre for the Replacement, Refinement and Reduction of Animals in Research) and the University of Strathclyde. Our overarching aim is to develop microfluidic technologies that will enable novel neuroscience research. With respect to Dementia-on-a-chip, this is undertaken as part of a consortium led by Selina Wray from the UCL Institute of Neurology (London, UK) that was successful in obtaining NC3Rs funding via their Crack It Challenge 12 called UnTangle. The aim of this challenge was to develop a physiologically relevant human stem cell-derived neuronal assay to predict the efficacy and unexpected pharmacological effects of new chemical entities and biologics targeting tau in Alzheimer’s disease. To this end, we have been utilizing patient-derived neurons using induced pluripotent stem cell (iPSC) technologies to investigate the consequence of tau mutations on neuronal development, function and maturity.

How do you anticipate this on-a-chip technology could be used to facilitate dementia research  and where do you see its biggest uses being?

“The benefits obtained from the microfluidic approach for these studies are numerous.”

The benefits obtained from the microfluidic approach for these studies are numerous. These include: the enhanced capabilities of controlling the fluid environmental parameters surrounding the cells; the higher control over the neuronal network patterning; the reduction of cell number (90% reduction) needed per assay; the ability to perfuse compounds of interest in an automated manner and with a throughput exceeding current capabilities; and the ability to monitor tau spread between co-cultures recreating pathological conditions found in vivo. Hence, utilizing this on-a-chip technology will allow us to provide an improved understanding of the mechanisms implicated in tau phenotypic variability and expression. Furthermore, we hope that this work will result in the development of an innovative and robust platform for patient-derived neuronal culture and drug screening that has the potential to be applied in other biological scenarios as well.

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