Abstract
Background & Purpose
Neurological drug development faces significant challenges, with 94% of drugs failing before or during clinical trials. Traditional models, including animal testing and 2D cell cultures, lack translational accuracy for neurological drugs, particularly in assessing peripheral neuropathy. The NerveSim® platform, a microphysiological system (MPS) developed by 28bio, provides a 3D tissue culture model that mimics in vivo nerve growth and functional electrophysiology. This system is designed to improve compound screening for neurotoxicity, neuroprotection, and neurorehabilitation.
Methods
- Model Setup: Peripheral nerve spheroids derived from rat dorsal root ganglia (DRG) cells or human induced pluripotent stem cells (iPSCs) were cultured.
- Electrophysiology Testing: Embedded electrode arrays (EEAs) were used to record compound action potentials (CAPs), measuring clinically relevant nerve conduction velocity (NCV), peak response amplitude (AMP), activity-dependent slowing (ADS), and threshold stimulus strength (TSS).
- Compound Screening: Neurotoxic compounds, including paclitaxel (PTX) and vincristine (Vn), were applied to assess their impact on neuronal function and electrophysiological responses.
Results
- Electrophysiology Testing: The system successfully measured functional nerve responses over time, allowing for longitudinal electrophysiological analysis.
- Neurotoxic Compound Effects: Paclitaxel and vincristine caused dose-dependent declines in electrophysiological metrics, demonstrating the system’s ability to detect peripheral nerve toxicity.
- Biological Significance: The platform provided clinically relevant insights into nerve fiber function, ion channel expression, and myelination, matching in vivo human nerve responses.
- Scalability & Automation: NerveSim® demonstrated high-throughput capabilities, making it ideal for drug screening applications.
Conclusion
The NerveSim® platform offers a highly translatable, electrophysiology-based system for studying peripheral nerve function and compound effects. Its ability to generate high-content electrophysiological data makes it a powerful tool for predicting drug-induced neurotoxicity and assessing neuroprotective compounds. Future studies will expand compound testing to build a predictive database for drug development.
