Jack Pribaz with his parents, Mike and Liz
As one of the nation’s leading pediatric epilepsy specialists, Douglas R. Nordli Jr., MD, has seen numerous advances in treating children with seizure disorders over the last 30 years. New medications, the ketogenic diet, nerve stimulators and neurosurgery have helped many of the more than 2,200 children with epilepsy seen each year by Dr. Nordli and his team at Ann & Robert H. Lurie Children’s Hospital of Chicago. Still, says Dr. Nordli, Head of the Division of Epilepsy, about 40 percent of patients do not respond to standard treatments.
Lurie Children’s epilepsy program has a robust research agenda focused on helping these treatment-resistant children. Its physician-scientists are collaborating with colleagues around the world on studies spurred by advances in genetics and DNA sequencing.
“These advances have revolutionized our understanding of why certain children have epilepsy,” says Dr. Nordli, the Lorna S. and James P. Langdon Chair of Pediatric Neurology. “Almost weekly, we learn of new gene defects that are responsible for epilepsy, opening up new possibilities for treatments. Research is so important, because at the end of the day if we’re not making the lives of our patients better, we’re not doing our job.”
Since the opening of Lurie Children’s on the campus of Northwestern University Feinberg School of Medicine three years ago, collaborations have blossomed between researchers at Lurie Children’s and their adult medicine counterparts at Northwestern. Dr. Nordli, co-leader of Northwestern’s new epilepsy research center, along with Northwestern researcher Alfred L. George Jr., MD, are collaborating on a study of the genetic role of sodium channel genes in childhood epilepsy. These are genes that are activated in the brain, influencing the normal firing of neurons. Of particular interest is the SCN1A gene, which is associated with several forms of childhood epilepsy and has more than 1,100 mutations.
Dr. Nordli says the project is benefiting greatly from electrophysiology technology at Northwestern that can screen 300 compounds simultaneously to determine their impact on cell function. This will be invaluable information for designing clinical trials at Lurie Children’s of new therapies targeting these sodium channels.
“Access to cutting-edge technology like this will increase our ability to identify exactly which epilepsy therapies will be most effective for a patient with a distinct genetic makeup,” says Dr. Nordli.
In a related project, Lurie Children’s epileptologist Linda Laux, MD, is sharing clinical data from more than 175 patients with Dravet syndrome treated at Lurie Children’s with colleagues at Northwestern. Dr. Laux cares for one of the largest groups of patients in the nation with this rare and treatment-resistant form of epilepsy that is associated with mutations in the SCN1A gene.
“Because we see so many of these patients, we can provide clinical information and patient samples vital in making the most accurate correlations with the hundreds of different sodium channel receptor mutations identified in Dravet syndrome,” says Dr. Laux. “This research will help us understand the disorder better and personalize treatment.”
Dr. Laux is also engaged in an FDA-approved study evaluating the safety, tolerability and efficacy of cannabidiol, derived from cannabis, in pediatric patients with Dravet syndrome. The study is supported by an award from the Northwestern University Clinical and Translational Sciences Institute.
Noted epilepsy researcher Anne Berg, PhD, of the Stanley Manne Children’s Research Institute, affiliated with Lurie Children’s, is a founding member of the Pediatric Epilepsy Research Consortium. This growing network of specialists representing more than 30 U.S. medical centers is focused on epilepsies affecting children early in life.
“By creating a large collaborative effort involving multiple centers, we hope to find treatments and improve care for the many rare and devastating disorders that comprise early life epilepsies,” says Dr. Berg. She is also the principal investigator of the Connecticut Study of Epilepsy at Yale University School of Medicine, which focuses on the social, educational and behavioral impact of epilepsy on children and their families.
Led by Dr. Nordli, Lurie Children’s is participating in two research projects as part of a federally funded consortium of more than 12 research centers focusing on Sudden Unexpected Death in Epilepsy (SUDEP), the largest cause of epilepsy-related deaths. Their goal is to identify factors such as genetic and brain structure irregularities that increase the risk of death. One project will focus on the creation of a surveillance registry to examine the characteristics of SUDEP cases versus survivors. The other is a translational research project to identify, validate and clinically evaluate predictive biomarkers and preventive treatments for SUDEP.
This article was originally published in the Fall 2015 issue of Heroes magazine.