NeuroTool

Disorders of the nervous system caused by drugs, environmental toxins, or pathophysiological processes can have far-reaching consequences, ranging from problems with signal transduction to loss of structural integrity of the neural network. Most of the research on these topics takes place in animals. Current in vitro systems are mostly limited to rodent neurons, with a few applications also using human neurons differentiated from stem cells (iPSC). The commonly used microelectrode arrays (MEA) are very expensive to consume, very limited in throughput, and so far have little standardization in their endpoints.

The NeuroDeRisk project, which has just been launched by the pharmaceutical industry and the European Commission, demonstrates the enormous need for innovation and practical applicability in toxicology. In other areas of biomedical research, the need is even greater. Here, a solution is proposed. Based on our already extensive and promising preliminary work, this project aims to bring to application maturity a robust, high-throughput, and comprehensive assay system for neuronal cell function. It is based on a human cell line of neuron precursors from which highly reproducible homogeneous, mature and functionally coupled neuronal cell cultures can be produced in a 384-well format.

Within the project, all relevant neurotransmitter receptors will be functionally characterized to precisely define the scope of application. The signals of individual receptors as well as the coordinated network activity will be recorded in an extremely reproducible and parallelizable manner using industry-relevant techniques such as Ca2+ fluorescence measurements. The cell cultivation methods for the development of a neural network will be developed in the central part of the project to the point where such a system can be made available to potentially interested parties as a robust test method with known acceptance criteria and performance parameters (based on well-characterized model substances).

In addition to this highly standardized basic test, modular extensions are offered. For example, cultivation as 3D organoids enables the detection of chronic substance effects or pathological processes. For the latter (e.g. neuroinflammation or metabolic disorders), the incorporation of glial cells and genetically modified neurons is also planned. These modules will be tested pharmacologically for their predictability. The project is rounded off by the documentation of test methods that meet regulatory requirements and an interlaboratory test, which pharmaceutical companies have also agreed to participate in.