Authors: Y. Ishibashi, N. Nagafuku, K. Kinoshita, A. Okamura, T. Shirakawa, I. Suzuki
Toxicology and Applied Pharmacology, 1 September 2023
Seeking alternatives to animal testing, scientists use Axion’s next-generation Maestro multielectrode array (MEA) platform to assess the neurotoxic effects of test compounds in vitro.
Evaluating compounds for neurotoxicity during drug development is essential to ensure patient safety and avoid costly delays. To avoid interspecies differences during testing, however, “an evaluation system based on a human-derived neural network that can act as an alternative to animal experiments is desirable…,” according to the authors. Research has demonstrated the usefulness of in vitro multielectrode array (MEA) assays for safety assessments and de-risking drug development but correlating initial MEA screening results with in vivo results has been challenging.
In this study, the authors describe an analysis method designed to reduce solvent effects from MEA analysis and extrapolate MEA results to in vivo responses to test compounds using co-cultured human-induced pluripotent stem cell–derived neurons and astrocytes. According to the authors, compared to other methods like patch clamping and calcium imaging, “MEAs are an ideal compound evaluation method to replace animal experiments as it is noninvasive, has a high time-resolution, enables multipoint measurement of electrophysiological activity of neural networks, and can evaluate changes in neural network activity caused by compound administration with high accuracy and medium throughput.”
First, the team used Axion’s Maestro multielectrode array (MEA) to assess seizurogenic potential of 10 test compounds, using principal component analysis to remove solvent effects. Concentrations producing hyperactivity via Maestro MEA were then compared to concentrations found in rat and human CSF during tremor and convulsion. The team concludes that their results demonstrate the utility of the Maestro to predict seizurogenic capacity and risk during drug development and that MEA assays may have the potential to replace animal experiments in the future.