A substance called Valproic acid (VPA) can be found in many neurotherapeutic drugs used to treat a variety of diseases, including the manic phase of bipolar disorder, seizures, and even migraines. But when taken during pregnancy, it has life-altering consequences on the evolving fetus. This has been widely known to researchers for quite some time now, but up until now, the reason remained unclear. Researchers from the Institute of Genetics and Molecular and Cellular Biology in France set out to find why VPA has such severe negative effects on fetal development.
What is VPA?
VPA is also used to treat depression and schizophrenia and is the most prescribed medicine for epilepsy. It was first synthesized in 1882 to be used as a non-reactive solvent, but in 1962, researcher Pierre Eymard discovered its anti-epileptic properties. Shortly after this discovery, VPA was approved for wide pharmaceutical use. Its activity blocks certain neurotransmitter passageways in the brain, eliminating or easing symptoms of neurological diseases.
Today it is commercially marketed under several different names, including Depakene, Depakote, Depakote DR, Depakote ER, Depakote Sprinkles, Stavzor, and Alti-Valproic.
There are many documented instances of pregnant women who use VPA giving birth to babies who suffer from several birth abnormalities, such as Spina Bifida (a condition that affects the spine and might cause physical and intellectual disabilities that range from mild to severe), facial changes, and heart malformations. Less frequent birth abnormalities include cognitive decline and Autism Spectrum Disorder.
Researchers found that stem cells responsible for building the fetal central nervous system undergo premature cellular aging after exposure to VPA. The researchers were also able to identify the specific molecule that caused the premature cellular aging. However, VPA continued to cause different birth abnormalities even in lab mice that don't have the gene that responds to the specific trouble-making molecule.
This premature cellular aging is known as senescence. "Cellular senescence has long been associated with aging and age-related disease," says Muriel Rhinn, the first author of the study. "We now show that aberrant induction of senescence can also contribute to developmental defects."