Common epilepsy drug disrupts early brain growth in human organoids after 30-day exposure

by Leonie Kroll, Karlsruhe Institute of Technology

edited by Lisa Lock, reviewed by Robert Egan

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It is known that the antiepileptic drug valproate increases the risk of developmental disorders in unborn children. A study conducted by the Karlsruhe Institute of Technology (KIT), the Heidelberg Academy of Sciences and Humanities, the University of Tübingen, and the University Heidelberg using lab-grown tissue models of the human brain gives new insights into the effects this drug has on early brain development. They open new avenues for research to mitigate the risk during pregnancy. The study has been published in Molecular Psychiatry.

With about 40 million patients, epilepsy counts among the most common neurological diseases worldwide. As a standard antiepileptic drug, valproate also plays a role in the treatment of bipolar disorders. Since it is known that valproate increases the risk of neurodevelopmental disorders, such as autism spectrum disorders, special warnings apply to women of childbearing age who take the drug. It has not been fully understood so far, however, how valproate actually affects the mechanisms of early brain development.

"We used lab-grown models of the human brain to investigate for the first time how the drug alters the extracellular matrix and how those alterations in turn affect processes within individual cells," said Zeynep Yentür, research assistant in Professor Simone Mayer's working group at KIT's Zoological Institute (ZOO).

The model system: Human brain organoids

For their study, the researchers used cerebral organoids, i.e., three-dimensional tissue structures grown from human stem cells, which served as models representing different development stages of the prenatal brain. They exposed these organoids to valproate for 30 days to simulate continuous exposure during the early development stages. Then, the researchers investigated the impact of the medication on the tissue, cellular, and molecular levels.

The results show that the drug significantly reduces cell proliferation, disrupts the ordered structure of critical development regions, and impairs the development of progenitor cells into mature neurons. The impact on the extracellular matrix is particularly strong, causing structural changes, increased stiffness, and impairment of intercellular communication and signaling processes, which are essential for normal brain development.

Despite the known risks, valproate is the only effective treatment option for certain female epilepsy patients. "With our research, we want to contribute to a better understanding of how the medication actually works to identify new avenues of research for mitigating the risk to fetuses," said Yentür. It is obvious that the findings from a lab study using tissue models cannot replace clinical data, but they do provide important insights into basic development mechanisms.

Publication details

Zeynep Yentür et al, Multiomics analysis identifies VPA-induced changes in neural progenitor cells, ventricular-like regions, and cellular microenvironment in dorsal forebrain organoids, Molecular Psychiatry (2026). DOI: 10.1038/s41380-026-03585-5

Journal information: Molecular Psychiatry

Key medical concepts

Valproic AcidExtracellular MatrixEpilepsyAutism Spectrum Disorder

Clinical categories

NeurologyPregnancyClinical pharmacologyWomen's healthObstetrics & gynecology Provided by Karlsruhe Institute of Technology Who's behind this story?

Lisa Lock

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