Postdoctoral research Claudia Persoon and professor Matthijs Verhage of Vrije Universiteit Amsterdam, developed new preclinical screening assays using functional, mature human neurons and CRISPR-Cas9 technology, to promote identification of promising treatment strategies for brain disorders. The use of human neurons, derived from patient skin cells, maximally approaches the situation in the patients’ brain in a tissue culture environment (‘patient-brain-in-a-dish’). High-end technology has been established to assess efficacy of novel therapies in these human neurons. Together, these assays provide new opportunities to develop successful treatments for brain disorders.
Brain disorders present a staggering health-care burden, costing around 800 billion euros per year in the EU and affecting almost 180 million people. Currently, development of treatments for these disorders is quite unsuccessful. Of all currently prescribed drugs, >30% target G-protein coupled receptors, that are typically activated by neuromodulators. Neuromodulators are signaling molecules secreted by most neurons, which regulate many processes in our brain and body. Dysregulation of neuromodulator secretion is firmly associated with many brain disorders, but no screening assay for neuromodulator secretion is currently available to develop new therapies.
For the ERC-PoC, Claudia Persoon and Matthijs Verhage have developed human-based neuromodulator screening assays for preclinical therapy design for brain disorders. This assay, the HumanNeuronScreen, uses human neurons, derived from patient skin cells, to maximally approach the situation in the patients’ brain and thereby greatly enhancing the validation of new therapeutic targets in preclinical research. It delivers in depth knowledge on the mechanism, potency and selectivity of candidate therapies, supporting a higher success rate for clinical trials. Therefore, this screen can drastically reduce costs of drug-development for pharmaceutical and biotech companies, and potentially impact 180 million patients in Europe. With this ERC proof-of-concept project, Claudia Persoon and Matthijs Verhage will show the commercial potential of the HumanNeuronScreen and perform all the necessary steps to make this new technology available for the drug development industry. This will maximize the impact of their scientific research conducted in the ERC Advanced grant DCV fusion, by bringing it from lab to market.