David Auerbach, PhD, assistant professor of pharmacology at Upstate Medical University, has been awarded a three-year $1.2 million grant from the National Institute of Neurological Disorders and Stroke to develop a research platform for the development and testing of medications that could help reduce and prevent seizures, and thus possibly prevent Sudden Unexpected Death in Epilepsy (SUDEP).

Epilepsy causes unpredictable seizures and other health problems. One in 26 people in the United States will develop epilepsy during their lifetime, and more than 1 in 1,000 people with epilepsy will die suddenly (SUDEP) each year. SUDEP is the most common disease-related cause of death with epilepsy.

Auerbach's lab works to advance the understanding of neuro-cardiac electrical disturbances.  Finding safe treatments for epilepsy is critical; people with epilepsy are at a 24-fold higher risk of sudden death.

“Oftentimes we focus a lot on the psychosocial comorbidities related to epilepsy; ‘If I have seizures I can't drive, it's hard for me to get to work,’” Auerbach said. “But the scariest point is these people are at a very high risk of sudden death, and to make it even scarier, oftentimes we don't know the underlying cause.” 

Researchers have found that some cases of SUDEP are linked to genetic variations related to heart rhythm problems, specifically Long QT Syndrome (LQTS). “Several years ago, with a large clinical database at the University of Rochester, I showed that there was a link between LQTS and an increased prevalence and risk of seizures,” explained Auerbach. “While we were excited about those results, we didn't understand the mechanism for it.”

LQTS Type 2 is caused by genetic variants in a gene called KCNH2, which produces a protein called K_v11.1. This protein is important for regulating the electrical activity of the heart and brain. People with LQT2 who also have epilepsy need effective medications to control their seizures. Up until now, there was a lack of models that accurately mimic LQTS-related epilepsy for research purposes.

“This grant will enable us to first demonstrate that this model reproduces the pathologies and abnormalities that are seen in people with this disease, then we can better understand the underlying causes,” he said.

The exact reason for seizures in LQTS isn’t completely understood, Auerbach noted. “We think that it may be due to the same mutant channel, not only being expressed in the heart but also expressed in the brain,” he said. “When it's expressed in the heart, it's messing up electrical function, so anywhere else where the expression has changed because of the mutation will likely result in electrical abnormalities as well.”

Auerbach says this research is crucial to safely treat patients. “You have to be very careful picking drugs because people with LQTS are very prone to electrical abnormalities in the heart.” Thus, this new model will enable his research team to evaluate the cardiac safety of neurotherapeutics. 

Additional grant support for Auerbach's work on SUDEP has come from CURE Epilepsy, a nongovermental organization working to uncover a cure for epilepsy through patient-focused research.