CMSRU Faculty Participate in Groundbreaking Epilepsy Study

Dr. Russell J. Buono and Dr. Thomas N. Ferraro, professors of Biomedical Sciences at Cooper Medical School of Rowan University (CMSRU), were part of a team of more than 100 epilepsy researchers from around the globe who collaborated on an important epilepsy research study that was published in the September edition of the prestigious periodical The Lancet Neurology.

The study analyzed the largest genome-wide association data set to date on DNA samples from epilepsy patients in order to identify the genetic influences on common forms of human epilepsy. Through their analysis, they successfully identified new genetic variants associated with common forms of the disease. This multinational collaboration of researchers organized and published as the Consortium on Complex Epilepsies under the umbrella of the International League Against Epilepsy (ILAE). 

The Consortium included epilepsy clinicians and researchers from the United States, Canada, United Kingdom, Ireland, Australia, Germany, Austria, Finland, Denmark, Italy and Hong Kong.

“The ILAE provided the necessary framework that allowed us to successfully collaborate on this unprecedented scale,” explained Buono.  “Because of the wealth of experienced and knowledgeable clinicians and researchers and the large number of samples that were analyzed, the power and significance of this study was greatly enhanced.”

Buono led the “Philadelphia Cohort,” which contains more than 2,000 epilepsy DNA samples collected by clinicians at Thomas Jefferson University Hospital, the Hospital of the University of Pennsylvania, The Children’s Hospital of Philadelphia, the University of Cincinnati, the University of Montreal, Harvard and Nationwide Children’s Hospital in Columbus, Ohio.  Buono and Ferraro are renowned epilepsy and genetic researchers, and they collaborated on a number of important studies before joining the faculty at CMSRU. 

The Lancet Neurology study, titled “Genetic determinants of common epilepsies: a meta-analysis of genome-wide association studies,” evaluated samples from nearly 9,000 patients diagnosed with epilepsy and more than 26,000 normal controls.  Two genes stood out as having broad implications for epilepsy.  One gene encodes a sodium channel subunit that regulates neuronal excitability (SCN1A) and has previously been associated only with certain familial and severe childhood epilepsies.  The Consortium study suggested that it may have an even broader role in common forms of epilepsy.  According to Ferraro, “This was not an unexpected finding given that most of the available anti-epilepsy medications work against sodium channels.”

Another gene (PCDH7) newly implicated in epilepsy by this analysis encodes the protein protocadherin, which helps brain cells bind together and communicate with each other.  This discovery was unexpected and suggests that the factors that contribute to common epilepsies are more complex than originally thought and may involve abnormalities in the basic cellular structure and early wiring of the brain.

According to Buono, this massive study highlights the complexity of the genetics of epilepsy as well as the importance of collaboration by multinational groups to better understanding of the many factors that contribute to the disorder.

“This study will definitely lead to more in-depth analysis of these genes.  Hopefully, we will soon understand why changes in these genes can increase risk for epilepsy.  Once we do, we will be one step closer to finding better diagnostics, treatments and perhaps even a cure for this debilitating condition,” he said.

Epilepsy is a chronic neurologic disorder, the hallmark of which is recurrent, unprovoked seizures.  It affects roughly one percent of the world population, not discriminating on sex, ancestry or geography.  Worldwide, 65 million people have been diagnosed with epilepsy, including more than two million Americans.  One third of people with epilepsy live with uncontrollable seizures because no available medication works for them.