Neurotoxicity is one of the major causes for adverse drug reactions and drug attrition during preclinical or clinical development, accounting for approximately 10% of all drug withdrawals regardless of therapeutic area .
This highlights the importance of improving risk assessment early in the drug discovery process and demonstrates the limitations of current animal models, which fail to clearly identify the risks of drug induced neurotoxicity in humans.
“Successful drug development processes should involve the implementation of in vitro approaches that can be utilized to address specific mechanistic questions around theoretical or identified neuropharmacological effects, whether detected during the development process or after approval. In vitro assays can also be used as screening tools to improve the chemical content and mitigate the potential neurotoxicity of future drug candidates, help to limit the number of compounds that are tested in vivo, reduce time and costs associated with neurotoxicity testing, and ultimately limit the impact that safety issues have clinically and with regard to withdrawal due to safety issues related to neurotoxicity.” 
Mechanistic neurotoxicity can be evaluated in vitro through the use of cultured neuronal models in traditional monolayer assay format, or with 3D neuronal organoids.
Assessment of neurotoxicity can be accomplished by assessment of cytotoxicity to neurons, activation of astrocytes, and evaluation of modulation of calcium signaling.
Molecular Devices ImageExpress Micro Confocal
High content screening
LIVE/DEAD fixable dead cell probe (Molecular Probes) DAPI (total cell count) Ca+2 probe GFAP Other markers available on request
Cell Model Type
3D cell models (e.g. tumor spheroids, organoids, etc.) or adherent monolayer / cell suspension
Cell Types Available
Neuronal monolayer format iPSC derived neural organoid (Stemonix) Custom models available on request
Test Article Concentration
8 point assay (0.05, 0.1, 0.5, 1, 5, 10, 50, 100 µM) (custom concentrations available) Single point assay