Towards safer epilepsy treatment for pregnant women

New research conducted in organoids is expected to provide pregnant women with epilepsy safer access to a common and highly effective anti-seizure medication, according to a study published in the journal Molecular Psychiatry.

Sodium valproate, or valproic acid, is widely prescribed for epilepsy and certain mental health conditions, but is considered harmful to use during pregnancy because of links to spinal cord defects and other complications for newborns. Dr Giovanni Pietrogrande and Professor Ernst Wolvetang, from The University of Queensland’s Australian Institute for Bioengineering and Nanotechnology (AIBN), have now led a team of organoid experts who have identified a drug that could nullify the dangerous side effects.

“We first set out to understand why valproate causes spinal cord malformations in fetuses,” Pietrogrande said.

“To do this we created organoids — human mini spinal cords in a dish — that closely mimic the spinal cord of a fetus in the early weeks of gestation.

“When these mini spinal cords were exposed to valproate, the team discovered that the drug changes the cells that normally form the spinal cord, leading to malformations.”

Wolvetang said the AIBN team then treated the organoids with the clinically approved drug rapamycin, and found it prevented the negative effects of valproic acid. “Therefore, co-treatment with rapamycin could be the thing that opens safe access to an extremely effective treatment for women with epilepsy,” he said.

Study co-author Professor Terence O’Brien, Head of the School of Translational Medicine at Monash University, said the findings could help healthcare providers and patients navigate the complex challenges around the treatment of epilepsy.

“It may also provide a pathway to enabling women to continue to take this life-saving medication while having healthy children,” O’Brien said.

Wolvetang said the research highlights the potential of new technologies like human stem cell-derived organoids to explore the molecular and cellular impacts of drugs. Indeed, he is separately involved in another study that will use brain and heart organoids to test newly developed anti-seizure spider venom peptides, which could be promising for those who do not respond to current anti-seizure medications.

“Organoids are a tool that allow us to develop new treatments, and also to uncover new ways to improve the safety and efficacy of existing ones,” Wolvetang said.

“We hope this research is another step towards fostering regulatory change in the Therapeutic Goods Administration (TGA) to establish organoids as a powerful tool for drug screening and discovery.”

Image caption: 3D high-resolution imaging of a spinal cord organoid.