Genes Influence Success of Pediatric Epilepsy Treatment
Variants of calcium channel blockers may dictate treatment response for pediatric epilepsy patients.
Many patients with various diseases fail to respond to conventional treatments, forcing them to experiment with other drugs and procedures to achieve disease control. This is applicable to patients with the most common form of pediatric epilepsy, childhood absence epilepsy (CAE).
CAE is characterized by seizures in which patients are unaware of their surroundings for a brief period of time, with some experiencing up to 100 per day. Patients are typically diagnosed between age 4 and 8. While some children stop experiencing the seizures, some go on to develop severe seizures.
A new study published by the Annals of Neurology discovered genes that may play a role in treatment response among children with CAE. These findings could be used in a precision approach to determine if a certain drug will effectively treat a patient.
“A better understanding of genetic factors underlying a disease and the way that people respond to treatments may help healthcare providers select the best therapies for children with CAE,” said Vicky Whittemore, PhD, program director at the National Institute of Neurological Disorders and Stroke.
The study authors explored whether genetics may be a driving factor behind the response to drugs commonly used to treat CAE, including ethosuximide, valproic acid, and lamotrigine. Specifically, the investigators looked at 3 genes that code for T-type calcium channels involved with the condition, and 1 gene that codes for the drug transporter that shuttles the drugs from the brain.
The new findings are part of a clinical trial that compares the effects of epilepsy drugs in 446 newly-diagnosed pediatric patients. The results could be used to predict which drugs would perform the best in certain patients, according to the study.
The authors discovered that 2 forms of the calcium genes were more common among patients who did not respond to ethosuzimide, while 2 other variants were found among patients who did not respond to lamotrigine, according to the study. Additionally, 1 variant of the drug transporter gene was commonly found among patients whose seizures continued.
After the gene variants were discovered, the authors continued exploring the calcium channel variant commonly found among patients who did not respond to ethosuximide.
When cells containing the calcium channel variant were exposed to ethosuximide, the drug was found to have little effect, according to the study. This finding suggests that the variant may influence drug response.
“We identified a potential link between genes and the childrens’ responses to certain treatments,” Dr Glauser said. “We were also able to clearly show that one variant caused a change in how a key calcium channel responded to ethosuximide, confirming what was found in the clinical trial.”
Additional studies are needed to study the specific genes involved with the disease itself and how it may impact drug efficacy, as well as determining other factors that play a role in treatment response, the study concluded.