Epilepsy is a disease that continues to hold on to its many secrets. Treatments for this complicated condition have remained the same for decades, and while anti-convulsant medications are good choices for children with mild epilepsy, they are often ineffective for children with more severe forms.
Ethan M. Goldberg, MD, PhD, attending physician and instructor in The Children’s Hospital of Philadelphia’s Division of Neurology, dedicates his current research to investigating the mysteries of how epilepsy works, in hopes of discovering an altogether new way to treat the condition.
“We don’t have great treatments. There are now 20 to 30 medications for epilepsy available, and they all follow the same basic principle in parallel with the generation of new anti-seizure meds, we need a whole new class of treatment, either cell-based or device-based, or something we haven’t thought of yet,” he says. “There are a lot of smart people who think epilepsy is curable. It’s a challenging problem, but an excellent one for neuroscience research.”
Goldberg’s research focuses on inhibitory interneurons, which are a rich and diverse group of cells that function to sculpt and control the electrical activity of the neurons around them. His interest is in the role these cells play in epilepsy.
“Our hypothesis is that the circuit dysfunction that underlies epilepsy is due to abnormal activities of different subtypes of interneurons,” he says.
Seizures by definition emanate from dysfunctional brain circuits, complex collections of interconnected neurons that process particular types of information such as memory traces or visual percepts. Interneurons make up only a small percentage of all neurons in a circuit, but nonetheless have critical functions in circuit operations. Seizures may be due in part to abnormal activity of these inhibitory interneurons. This abnormal activity leads to disinhibition, allowing seizures to hijack neural circuits by facilitating hyperactive self-sustaining electrical discharges.
Goldberg’s research uses advanced methodological approaches such as optogenetics, multicellular imaging and multiple whole-cell electrical recording to track and manipulate the activity of interneurons while monitoring the large-scale activity of neural circuits, in an attempt to identify and modify dysfunctional epileptic circuits. “Our group is one of the few in the country applying cutting-edge neuroscience techniques to study epilepsy,” he says.
CHOP’s Research Institute and collaborative atmosphere allow Goldberg and his collaborators to actively and aggressively seek answers to their most complex questions. “We have a great dialogue across disciplines, including neuroscience, pediatric and adult neurology, developmental biology, and psychiatry. People are very committed to epilepsy research and very interested in translational science.”
Thinking ahead, Goldberg is pursuing a cell-based therapy for epilepsy in collaboration with Stewart Anderson, MD, at CHOP. “A cell-based therapy using interneuron precursors would be an example of something tailored to the underlying causes of epilepsy,” Goldberg says. “I take care of kids with difficult-to-control epilepsy. I am trying to understand the mechanisms of their disease. And I hope to bring my findings back to the clinic to help my patients.”