Drug treatment alters performance in a neural microphysiological system of information processing

(Press-News.org) In a world-first breakthrough, researchers have used an epilepsy-like disease model in a laboratory dish and showed that improved information processing and neural function can be achieved using a medication designed specifically to treat the disease. Published in Communications Biology, the research was led by Cortical Labs and marks a significant breakthrough in the study and treatment of neurological disorders in real time.   

 

Cortical Labs is an Australian start-up which created the world’s first commercial biological computer, the CL1, which fuses lab-cultivated neurons from human stem cells with hard silicon to create a more advanced and sustainable form of AI, known as “Synthetic Biological Intelligence” (SBI).  

 

Alongside Cortical Labs, the research was conducted by researchers from the University of Cambridge and UK-based biotech startup bit.bio.

 

Brett Kagan, Chief Scientific Officer at Cortical Labs, commented: “This breakthrough is a major step forward in not only how we study and understand diseases and drugs that are designed to treat related neural processes impacted by these diseases. For the first time, alongside some of the world’s most eminent researchers in their field, we’ve been able to show that impaired information processes a disease in a dish can be restored using a drug designed specifically to treat it.

 

“While this is an incredibly significant milestone, and the realisation of years of focus at Cortical Labs, it’s only the start. The ability to observe how living neurons react to real-time stimulation and drug treatment opens up entirely new ways to develop, test, and personalise therapies – all without relying on animal models. Based on our early findings, we’ll continue to refine the modelling with the aim of developing more effective, patient-specific therapies in the future.”

 

Assessment of pharmacological intervention on in vitro neural systems often emphasises molecular and structural changes. However, neural systems fundamentally process and act on information. For preclinical assays to predict drug efficacy, they must model these physiological functions. 

 

DishBrain, an in vitro synthetic biological intelligence (SBI) assay embodying a neural system in a simulated game-world, enables the quantification of this information-processing capacity, however the question remains whether such a system permits classical pharmacological interrogation and dose-response profiling. 

 

Hyperactive glutamatergic dysregulation is linked to neurological disorders including epilepsy, and inducible overexpression of neurogenin 2 (NGN2) in human induced pluripotent stem cells (hiPSCs) generates glutamatergic cultures with dysregulated hyperactivity. 

 

The research, therefore, tested three anti-seizure medications (ASMs), phenytoin, perampanel, and carbamazepine, on NGN2 neurons from day 21 of differentiation in this system. The ability to use these reproducible cell types was enabled by key collaborators University of Cambridge and UK-based biotech startup bit.bio. The key finding was that, while all compounds altered spontaneous firing, carbamazepine 200 µM significantly improved gameplay metrics. 

 

This marks the first demonstration of altered SBI following exogenous drug treatment. Notably, only inhibitory compounds enhanced goal-directed activity, linking glutamatergic attenuation to performance. Neurocomputational analysis revealed nuanced pharmacological responses during closed-loop stimulation, highlighting insights beyond spontaneous activity metrics.

 

Brad Watmuff, Head of Biology at Cortical Labs, commented: "One of the most pressing challenges in neuroscience is improving the success rate of effective new treatments reaching patients. Our work highlights a key obstacle to this goal — that the neural functional endpoints we typically rely on to define treatment efficacy may not be optimal. Importantly, we show these endpoints can be influenced and even improved with drug intervention, opening the door to more meaningful measures of therapeutic success."

 

The research was conducted by Bradley Watmuff, Forough Habibollahi, Candice Desouza, Moein Khajehnejad, Alon Loeffler, Koby Baranes, Noah Poulin, Mark Kotter and Brett J. Kagan.

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