Optimal In Vitro Screening Approaches for Detecting Early CNS Liability

Over the course of the next few weeks we will be sharing some of our research due to be presented at SOT 2020 which was cancelled as a result of the COVID-19 outbreak. In this blog, we present the highlights from our poster titled: ‘Assessing the Differential Sensitivities of a Microelectrode Array Assay and a Neurite Outgrowth Assay for Detecting CNS Liabilities Using a Set of Neurotoxic and Seizurogenic Compounds’.

The introduction to this poster starts with a tragic story related to the neurotoxin, domoic acid, which hit the headlines in 1987 after it was linked to the poisoning of 107 people and the subsequent death of 3 people on Prince Edward Island in Canada. The cause was found to be related to amnesic shellfish poisoning from the consumption of domoic acid-contaminated mussels harvested from the Prince Edward Island river estuary.

In the laboratory, domoic acid acts as a valuable reference compound as it completely eliminates spontaneous spike activity at concentrations ≥ 1 μM within a MEA system yet has no effects on neurite outgrowth or cell health up to 25 μM over 72 hr. Our research exams this phenomenon further by evaluating a broader set of known neurotoxic and seizurogenic compounds and compares their sensitivities within a microelectrode array assay and a neurite outgrowth assay.

Interestingly, five of the compounds tested exhibited CNS liabilities at significantly lower concentrations in the MEA assay compared to the neurite outgrowth – mimicking the effect seen with domoic acid. Four of the compounds exhibited similar results in both assays whereas three compounds exhibited greater sensitivity in the neurite outgrowth assay compared to the MEA assay.

The results from this study clearly highlight the importance of implementing a combined screening strategy utilising the MEA assay in addition to a neurite outgrowth assay to capture CNS liability generated through different electrophysiological and non-electrophysiological mechanisms.

Download our poster to learn more

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