NEUREKA merges advanced computational modelling and high throughput nanoelectrodes into a powerful hybrid. The proposed merge allows the brain-mimicking control of activity and the realistic modelling of neural diseases in culture, thus leading the way for a new generation of dish trials. The proposed NEUREKA device will bring a paradigm shift in drug discovery for neurological diseases, a sector that suffers multiple, repeated failures exacerbating the economical and societal burden of these incurable diseases. It will do so by addressing a crucial shortcoming: the lack of in vitro systems faithfully reproducing brain pathology that enable the functional assessment of candidate compounds at multiple levels: from synapses to neuronal circuits.
NEUREKA introduces an innovative, hybrid technology, whereby detailed, computational neuronal networks simulate dysfunction and drive cultured neurons to replicate in-brain disease conditions. Nanoelectrodes will mediate the transmission between simulated and biological neurons in a closed loop. Nanoelectrodes are akin to real synapses. They contact cultured neurons at subcellular locations across the dendritic tree, soma and axonal branches, allowing control and monitoring of neural activity with unprecedented precision. Biological neuronal responses registered by nanoelectrodes are fed back to simulated neurons, closing the loop and enabling control of activity states across the hybrid population.
Computational modeling enables the replication of both molecular and physiological deficits of neurodegeneration in vitro by complementing the molecular deficits already present in culture models. The cultured neurons will be driven towards pathological excitability states where deficits emerge, so as to optimize quantification of the impact of drugs, going well beyond standard cellular assays. A proof-of-concept will be provided for Alzheimer’s disease, using human induced pluripotent stem cell (iPSC)-derived neurons exhibiting the pathology. NEUREKA will be used to demonstrate the effect of drug candidates across synaptic, neuronal and network functions.
NEUREKA is an EU H2020 Future and Emerging Technology. A partnership between Foundation of Research and Technology-Hellas (FORTH), Universita degli Studi di Padova, Laboratoire d’Analyse et d’Architecture des Systèmes (LAAS-CNRS), Università degli Studi di Milano-Bicocca and Maxwell Biosystems.
A smart, hybrid neural-silico-computo device for drug discovery
A visionary and innovative hybrid technology, whereby nanoelectrodes and sophisticated computational models of neuronal circuits are combined to readout and manipulate activity/connectivity in cultured neuronal networks of Alzheimer’s disease, with subcellular accuracy