Scientists have made a breakthrough toward a genetic test that could help thousands of mothers with epilepsy safely take life-saving medication without fear of it causing birth defects in their children.
Valproic acid (VPA) is an anti-seizure medication, and for many people with epilepsy it is the only or most effective treatment.
But several countries are increasingly restricting its use because around 10 per cent of babies born to mothers who take VPA during pregnancy have a structural birth defect, the nature of which can range from severe neural tube defects to milder defects such as cleft palate.
The research, led by Monash University alongside Australian and international researchers and the Raoul Wallenberg Australian Pregnancy Register, has been published in the academic journal Neurology.
It identified a type of DNA sequence variation in mothers that can modify the risk of their child being harmed if they take VPA during pregnancy, and found that VPA affects the function of molecules which bind to DNA and regulate the activity of genes during fetal development.
Genetic variants within a mother’s DNA can affect this binding process, explaining why the drug only increases the risk of an adverse effect in some fetuses.
Lead researcher Dr Alison Anderson, a bioinformatician and Research Fellow in Monash’s School of Translational Medicine, said the team is working on developing a genetic test to identify who could safely take VPA because they do not have the genetic risk of birth defects during pregnancy.
“This is a critically important problem we need to solve, because clinicians need to weigh the risks for infants exposed to epilepsy medication such as valproate in the womb against the risk of injury or even death in the mother due to uncontrolled seizures if they don’t take the medication, or take a less effective drug,” Dr Anderson said.
“For some women valproate is the only medication that controls their seizures.
“What we want to do is ensure those people who have no genetic risk for birth defects from valproate can continue taking the medication.”
Senior researcher Professor Terence O’Brien, an internationally renowned neurologist and epilepsy expert in the Monash School of Translational Medicine and at Alfred Health, said the study highlighted the importance of registries as a critical source of data for researchers.
“This collaboration has used data from pregnancy registries in Australia around the world, which give us unparalleled insights into how pregnant women with epilepsy and their babies fare on and without medication,” Professor O’Brien said.
“This information is critical in taking us closer to the day when we can offer precision medicine for this group, being able to predict responses to medications, based on a patient’s specific genetic makeup, rather than trial and error.”
A separate study led by the same group of researchers at Monash University, published in Neurology in November, used deep learning models to integrate and analyse genomic data and clinical information to predict response to first-line treatments in people with newly diagnosed epilepsy.
The next phase of the research will involve the use of the latest deep learning tools for predicting the effects of genetic variants on drug therapy and adverse effects, to be enabled by Australian-first technology with the activation of the University’s MAVERIC supercomputer this year.
Read the research paper: https://doi.org/10.1212/WNL.0000000000214570
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