Duke researchers will collaborate in a global $25 million grant to study the genetic basis of epilepsy.
The Center without Walls initiative seeks to unite researchers from institutions around the globe to use genetics to explain the causes of epilepsy and to prescribe more tailored treatment. The National Institute of Neurological Diseases and Stroke, part of the National Institutes of Health, funded the collaborative effort as part of the Epilepsy Research Benchmarks NINDS set in 2000 to target the prevention and treatment of epilepsy.
In the next five years, more than 20 investigators from Europe, the United States and Australia will analyze the genomes of 4,000 epilepsy patients from around the world, said David Goldstein, director of the Duke Center for Human Genome Variation and an investigator in the study.
“This is one of the first large-scale sequencing studies in a common disease, the first in neuropsychiatric disease,” Goldstein said.
The study aims to use the genetic basis of epilepsy to shed light on how epilepsy works in general, which will help physicians better design physiological and psychological treatment of the disorder, said Dr. Rodney Radtke, medical director at the Duke Sleep Disorders Laboratory. Radtke will contribute to the study by identifying subjects and assuring the accuracy of their epilepsy diagnosis. Understanding the genetic factors in epilepsy will also help physicians personalize the drug combinations for individual patients, Radtke added.
“By knowing the genetic basis of epilepsy, we will be even better at designing more effective treatment,” Radtke said.
Epilepsy affects 50 million people worldwide, according to the World Health Organization. The Centers for Disease Control and Prevention estimate two million people have epilepsy in the United States. This disorder is characterized by unpredictable loss of consciousness due to uncontrolled activity of brain signals.
The seizures are not usually fatal, Radtke said in an email Sunday, but the unexpected loss of consciousness from epileptic seizures complicates patients’ lives through increased likelihood of falls and motor vehicle accidents, loss of self-confidence, employment challenges and general social stigma. Additionally, approximately one in 500 to 1,000 epilepsy patients per year pass away due to a sudden unexpected death in epilepsy—when a patient with epilepsy dies without an apparent medical reason.
Current epilepsy treatment include medication and surgery. There are about 15 anti-epilepsy drugs available, Radtke said, noting that through trial and error, the physician finds the best combination for individual patients.
“Even with the best effort, about one-third of epilepsy patients still suffer from unpredictable seizures,” Radtke said.
The surgical options involve cutting out parts of the cortex, the part of the brain that contributes to seizures, he added.
The Duke CHGV, which has established an infrastructure for sequencing and interpreting patient genomes, will lead the sequencing effort in the NINDS initiative, Goldstein said. The University of California, San Francisco is responsible for characterizing the clinical phenotypes of patients, and other collaborators will investigate individual epilepsy syndromes. Dr. Daniel Lowenstein at UCSF and Dr. Samuel Berkovic from the University of Melbourne will administrate the Center without Walls, along with Goldstein.
“The researchers will likely find additional [genetic] factors that we didn’t know about, but I think it will be very complicated to sort out which genetic variations contribute to the disease,” Fureman said.
Future grants could investigate the environmental and epigenetic factors of epilepsy, she added.
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