Sodium valproate is an effective epilepsy drug but is not recommended during pregnancy
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The drug rapamycin prevents the epilepsy drug valproate from causing developmental problems during pregnancy.
Sodium valproate is used to treat epilepsy, bipolar disorder, and sometimes migraines. Although effective, it is not recommended for use during pregnancy as it can lead to congenital conditions such as spina bifida and lifelong learning difficulties.
Giovanni Pietrogrande A professor at the University of Queensland in Australia and his colleagues wanted to understand why sodium valproate had such an effect. So they used stem cells to create miniature spinal cords, called organoids, in the lab. They mimic the spine of a fetus in the first weeks of pregnancy.
When organoids are exposed to sodium valproate, their cells undergo changes that may be linked to the risk of congenital disease.
To explore why, the team found that the activity of one of the cells’ signaling pathways, called mTOR, indicates they are undergoing aging. During this process, cells stop proliferating but do not die, but continue to release chemicals that can cause inflammation.
Rapamycin was originally developed as an immunosuppressant but has shown some promise for its anti-aging effects by also targeting the mTOR pathway.
In another experiment, the researchers exposed a new group of spinal cord organoids to a combination of sodium valproate and rapamycin and found that senescence did not occur. They then repeated the test in zebrafish larvae and also found that the cells did not enter a senescent state or show signs of the changes that occurred when the cells were exposed to sodium valproate alone.
Doctors won’t tell epilepsy patients who are pregnant or may become pregnant to stop taking valproate, but one day we may be able to prevent its negative effects by combining valproate with rapamycin, Pietrogrand said. People need to be researched before recommendations can be made.
Frank Wajda The University of Melbourne says valproate is a “very important drug and the most effective treatment for generalized epileptic seizures”, when abnormal electrical activity occurs in both halves of the brain at the same time.
“I think this is a very important paper that may lead to this drug returning to its level of importance before its side effects were discovered,” he said.
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