NeuroTool

Disorders of the nervous system, caused by drugs, environmental toxins or pathophysiological
processes can have far-reaching consequences, ranging from signal transmission problems
to the loss of structural integrity of the neural network. Most of the research on these issues
takes place in animals. Current in vitro systems are mostly restricted to rodent neurons,
a few applications also use human neurons differentiated from stem cells (iPSC). The often
applied microelectrode arrays (MEA) are very expensive in consumption, very limited in
throughput, and so far little standardized 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. The
need is even higher in other biomedical research fields. A solution is proposed here. Based
on our already extensive and promising preliminary work, this project aims to bring a robust,
high-throughput and comprehensive test system for neuron function to application
maturity. It is based on a human cell line of neuron precursors, from which highly
reproducible homogeneous, mature and functionally coupled nerve cell cultures in 384-
well format can be produced. In the project, all relevant neurotransmitter receptors will be
functionally characterized in order to precisely define the application domain. The signals of
single receptors as well as coordinated network activity will be recorded extremely reproducible
and parallelizable 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 such an extent that such a system can be made
available to potential 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 will be offered. For
example, the cultivation as 3D organoids allows 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 predictivity. The project is rounded off by test
method documentation that meets regulatory requirements and an interlaboratory test
for which pharmaceutical companies have also agreed.