Understanding gene variants in early-onset epilepsy

Children with epilepsy don’t respond to treatment as well as adults. To understand why, Dr. Tracy Gertler is investigating the genetic origins of the disease that give rise to aberrant neural activity. Armed with this insight, Gertler plans to develop more targeted therapies based on each child’s genetic profile. View Halo Profile >>

Tell us about your research…

My research incorporates a three-tiered physiological approach to integrating the molecular, cellular, and circuit-level impact of genetic variants implicated in epilepsy. As a pediatric neurologist focused on neurogenetics, my work represents a mechanistic counterpart to clinical interpretation of inherited and de novo pathogenic variants in children with epilepsy using a reduced cell-based system, patient-specific stem cell-derived neurons, and transgenic mouse models of epilepsy.

My research incorporates a three-tiered physiological approach to integrating the molecular, cellular, and circuit-level impact of genetic variants implicated in epilepsy.

By focusing on patient-specific genetic variants, my research replaces the stigma in the rare disease arena of small cohorts and limited technological advance with the idea that precision therapies are not only necessary for individuals but also key insights toward identification of critical pathways and novel drug targets in epilepsy and neurodevelopmental disability.

By focusing on patient-specific genetic variants, my research replaces the stigma in the rare disease arena of small cohorts and limited technological advance

Can you explain that to a non-scientist?

As we learn more about the causes of epilepsy, it is becoming apparent that changes in our DNA, the genetic code which dictates how our bodies function, are often the cause. Because many children do not respond to conventional epilepsy medications, it is critical to understand not only the cause of epilepsy, such as a bad gene, but the ways in which the affected gene causes cells in the brain to miscommunicate so that we may develop new targets for medication.

Because many children do not respond to conventional epilepsy medications, it is critical to understand…the ways in which the affected gene causes cells in the brain to miscommunicate.

How could it someday impact patient lives?

Epilepsy is among the most common childhood neurologic disorders, affecting 40 children per 100,000 in the U.S. alone. The availability of gene panels and of whole-exome sequencing have dramatically improved etiologic diagnoses of early-onset epilepsy, as 30-50% of early-life epilepsy is now associated with pathogenic gene variants. The long-term goal of my work is to be able to identify genetic epilepsy early in life, define its pathogenic mechanism in a neuron, and precisely apply medication targeted to the aberrant neuronal activity.

The long-term goal of my work is to be able to identify genetic epilepsy early in life, define its pathogenic mechanism in a neuron, and precisely apply medication targeted to the aberrant neuronal activity.

In addition to her role at Lurie Children’s Hospital, Dr. Gertler is also an Instructor at the Northwestern Feinberg School of Medicine.