PhD Defense: Exciting Models

Exploring the Applicability of Human Neuronal Cell Models for In Vitro Neurotoxicity Screening and Seizure Liability Assessment

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Thesis summary: 

Regulatory authorities require that medication is extensively tested by pharmaceutical companies before it can enter the market. They want to be sure that the compound is not neurotoxic nor cause potentially life-threatening seizures, a frequently observed side effect. Seizures are periods in which brain cells are hyperactive. Tests are often performed on animals or with animal tissue. However, current tests are not predictive enough for human risk as is reflected in the high drug attrition rate. Also, animal experiments are time consuming, expensive and ethically debated. Therefore, this project aimed at developing an alternative test method for the detection of seizures. 
We used human brain cells, to circumvent inter-species translation. It is now possible to make many human brain cells from a very small piece of human skin. The main task of brain cells is to communicate by sending and receiving signals. We combined the human brain cells with a state-of-the-art technique, the micro-electrode array (MEA), allowing us to measure the normal level of communication before and after exposure to a seizurogenic compound. If the level of communication increases, the added compound is likely to cause a seizure. 
In this project we showed that human brain cells form communicating networks and that activity levels increased when adding seizurogenic compounds. This a promising and essential step towards animal free neurotoxicity testing. Now we need to expand the data set so we can demonstrate that these human brain cells are better in predicting adverse effects than animals.

Start date and time
End date and time
Location
Digital
PhD candidate
A.M. Tukker
Dissertation
Exciting Models. Exploring the Applicability of Human Neuronal Cell Models for In Vitro Neurotoxicity Screening and Seizure Liability Assessment.
PhD supervisor(s)
Prof. dr. ir. J. Legler
Co-supervisor(s)
Dr. R.H.S. Westerink