The Link Between Migraine Therapy and Premature Fetal Aging
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.
Research findings
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."