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Innovative Drug Therapy Demonstrates Promise in Laboratory Neuron Models of Epilepsy

Innovative Drug Therapy Demonstrates Promise in Laboratory Neuron Models of Epilepsy

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Researchers have demonstrated that targeted drug treatments can improve neural function in laboratory models of epilepsy, paving the way for personalized therapies and advanced neurological research.

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In a groundbreaking breakthrough, scientists have successfully modeled an epilepsy-like condition in laboratory-grown human neurons and discovered that targeted drug treatments can significantly improve neural function and information processing within this system. This pioneering research, published in Communications Biology, led by Cortical Labs, marks a substantial advancement in understanding and developing therapies for neurological disorders.

This study utilized neurons derived from human induced pluripotent stem cells (hiPSCs) engineered to overexpress neurogenin 2 (NGN2), which induces hyperactive glutamatergic activity associated with epilepsy. Researchers tested three anti-seizure medications (ASMs)—phenytoin, perampanel, and carbamazepine—on these NGN2 neurons from day 21 of differentiation. While all drugs influenced spontaneous firing rates, carbamazepine at 200 µM notably improved the performance of the neurons in a simulated game environment, indicating enhanced functionality.

Remarkably, this study is the first to demonstrate that drug treatment can alter the behavior of synthetic biological neural systems (SBI) in a measurable way. The findings revealed that only inhibitory drugs increased goal-directed activity, establishing a direct link between glutamatergic attenuation and improved neural performance. Neurocomputational analysis provided deeper insights into pharmacological responses during real-time stimulation, beyond basic activity measures.

Brett Kagan, Chief Scientific Officer at Cortical Labs, emphasized the significance of this research: "This advancement allows us to observe how living neurons react to drugs and stimulation in real time, opening new avenues for developing personalized and more effective therapies without relying on animal models. Our ongoing work aims to refine these models further, bringing us closer to tailored treatments for neurological diseases."

The research underscores a shift towards functional, information-centric neural assays for preclinical drug testing. Traditional molecular and structural assessments may overlook critical physiological processes, but modeling neural information processing helps predict drug efficacy more accurately. This study contributes vital knowledge to the field, particularly regarding hyperactive glutamate signaling in epilepsy and related disorders.

This research was conducted by a collaborative team from Cortical Labs, the University of Cambridge, and biotech startup bit.bio. The findings suggest that utilizing reproducible neuron models in conjunction with pharmacological testing can significantly enhance our understanding of neural drug responses and accelerate therapeutic development.

For more detailed information, see the original publication: Communications Biology.

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