Spinal cord organoids could enable safer treatment for pregnant women with epilepsy

Researchers at the University of Queensland have taken an important step towards providing women with epilepsy with safer access to a common and highly effective anti-seizure medication.

Sodium valproate or valproic acid is widely prescribed for epilepsy and some mental health conditions, but its use is considered unsafe during pregnancy due to links to spinal cord abnormalities and other complications in new-borns. -born.

Dr Giovanni Pietrogrande and Professor Ernst Wolvetang from UQ’s Australian Institute of Bioengineering and Nanotechnology (AIBN) led a team of organoid experts who identified a drug that could reverse dangerous side effects. The research is published in the journal Molecular Psychiatry.

“We first sought to understand why valproate causes spinal cord malformations in fetuses,” Dr. Pietrogrande said. “To do this, we created organoids – mini human spinal cords on a plate – that closely mimic the spinal cord of a fetus during the first 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.

Professor Wolvetang said the AIBN team then treated the organoids with the clinically approved drug rapamycin and found that this prevented the negative effects of valproic acid.

“Therefore, co-treatment with rapamycin could open up safe access to highly effective treatment for women with epilepsy,” said Professor Wolvetang.

Study co-author Professor Terence O’Brien, director of the School of Translational Medicine at Monash University and program director and deputy director of research at Alfred Brain, said the findings could help Healthcare providers and patients address the complex challenges of treating epilepsy.

“It could also allow women to continue taking this life-saving medicine while having healthy children,” Professor O’Brien said.

Professor Wolvetang said the research highlights the potential of new technologies such as human stem cell-derived organoids to explore the molecular and cellular impacts of drugs.

“Organoids are a tool that allows us to develop new treatments, but also to discover new ways to improve the safety and effectiveness of existing treatments,” he said. “We hope this research is another step toward promoting regulatory change within the Therapeutic Goods Administration (TGA) to establish organoids as a powerful tool for drug screening and discovery.”

Provided by the Australian Institute of Bioengineering and Nanotechnology (AIBN)