Cell Analysis
Jun 30, 2023
| 4 min read

Reshaping Neuroscience Drug Discovery with iPSC-Derived Neuron Models

There is a significant unmet need for new treatments that target diseases of the central nervous system (CNS). Drug candidates in this area have a high failure rate, highlighting the importance of predictive disease models that help scientists advance better leads. In this blog, we feature part of an exclusive interview with Dr. Emma Jones, Lead Scientist and Dr. Eve Corrie, Scientist of In Vitro Neurobiology at Medicines Discovery Catapult, about their work in developing complex in vitro CNS models for drug testing.

This article is posted on our Science Snippets Blog  


 

Medicines Discovery Catapult supports neuroscience drug discovery by developing physiologically relevant human CNS models, including human iPSC-derived neurons, astrocytes, and microglia. They use these complex culture systems to look at the effects of drugs on a variety of cell behavior, such as neurite outgrowth, excitotoxicity, and neuronal activity. Here is a preview of our exclusive interview with Dr. Emma Jones and her team about their exciting work.


Developing a platform to test potential central nervous system treatments requires working with neurons, which are known to be fussy cells. What challenges do you face when working with neurons?

“In thinking about the end goal, our first challenge is creating neuronal models that are physiologically relevant and predictive. So, we’re thinking about what type of neurons we have; are they glutamatergic or inhibitory neurons? Or what culture properties do we need to model different CNS diseases? So that could be done either using cells that have disease-causing mutations or by stimulating the cells with different kinds of stress or disease-causing stimuli.

Next, are the technical issues of working with neurons, which are quite challenging. To get healthy, reproducible cultures in vitro that are at the right maturity, we need to optimize the growth conditions. So, we think about the type of media and try monocultures or co-cultures with different cell types, such as astrocytes, whilst also thinking about their attachment to the dish.”
 

In the video, you talked about using the Incucyte® system. How do the capabilities of the Incucyte® system support the types of experiments you do in your lab? 

“We're interested in how cultures mature over time. What's nice about Incucyte is that we can take continuous measurements over time, where the cells are maintained in the proper CO2 and temperature conditions. It really allows us to track electrical activity and look at different time points. So, for example, we can add drugs and look and see how they affect activity or observe activity as the circuitry matures.”
 


Can you walk us through a recent experiment or project where you used the Incucyte® to study neurons, and what insights or outcomes did you gain from the data?  

“We do many collaborations with small biotech companies that want to know if their drug can modulate neurite outgrowth, while simultaneously monitoring neuron viability. For these types of experiments, we plate iPSC-derived neurons with a concentration range of the therapeutic and then monitor the outgrowth of neurons. We can measure outgrowth from the branching dynamics and monitor possible toxic effects of the drugs at the same time.”


Looking ahead, what are some of the key research questions or areas of focus that you hope to address with the help of the Incucyte, and what do you see as the potential impact of this work on the field of neuroscience and drug discovery?

“We want to help companies validate their targets more efficiently and with more information. To do that, our goal is to have the best CNS models that are robust, reproducible, and predictive. In terms of neural activity, we are continuing to build on the models we have by using different types of iPSC-neurons or culture systems, such as incorporating inhibitory neurons with glutamatergic neurons or using neurons with disease-causing mutations. We are also working with tri-cultures of human iPSC-derived neurons, astrocytes and microglia, and plan to look at the activity of those cultures.”

Advanced cell models have been a hot topic lately. More biological relevance means better prediction of toxicity and other attributes that can cause a drug candidate to fail. This is why the work of Dr. Jones is so important in helping to speed up the drug discovery process. 

One of the technologies that supports this important work is Incucyte® Live-Cell Analysis. With this system, you can set up cell culture assays, like a neurite outgrowth assay, and automatically collect images in real time, without ever removing the cells from the culture hood. To learn more, be sure to read the full interview for additional insights from Dr. Jones and Dr. Eve Corrie on this fascinating area.

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