Unravelling the mystery of treatment-resistant epilepsy
Epilepsy is a devastating neurological disease that affects one in 200 children and adolescents in Canada, causing seizures that can occur sporadically or daily. Thirty to 40 per cent of patients do not respond to drug treatments or stop responding after initial success.
A University of Alberta researcher is hoping to shed light on treatment-resistant or refractory epilepsy. If the team in Qiumin Tan’s lab is successful in learning more about the etiology — or cause — of this sub-set of the disease, it might someday lead to new management strategies. Children and adolescents whose epilepsy is not well-controlled are at a higher risk of death from the disorder and are more likely to have learning disabilities, depression, anxiety and other problems.
“Refractory epilepsy really affects every single aspect of their lives,” says Tan, an assistant professor in the Department of Cell Biology and Canada Research Chair in Molecular Genetics of Human Disease. Funding for her lab includes a WCHRI innovation grant and a partnership grant that enabled her Canadian Institutes of Health Research Early Career Investigator Award.
Epilepsy presents a complex challenge to researchers because it is caused by many different mechanisms that disturb brain circuitry. “The etiology is not simple,” explains Tan. “We cannot attribute it to one single cause.”
Her research is focused on Cajal-Retzius cells, nerve cells that are normally found in the brain only during embryonic development, dying off once they’ve completed their work. However, these Cajal-Retzius cells have been found in the brain tissues of patients undergoing epilepsy surgery, leading Tan’s research team to question why they lingered and if that could contribute to seizures in refractory epilepsy.
While Tan’s research is at the most fundamental stage at this point, it could contribute to future epilepsy management. If researchers can understand why these cells are not dying and if their persistence contributes to seizures, future technologies could be developed to either silence or activate the cells, which might help with seizures, she explains.
To study these Cajal-Retzius cells, Tan and her research team are using a lab model they developed for another major research project in which they are investigating a rare neurodevelopmental disorder caused by a mutation in the capicua (CIC) gene. Thirty to 40 per cent of people with the CIC mutation also have epilepsy.
There are very few patients in the world with the CIC disorder. One of them is Seta Atamian’s 26-year-old daughter Natalie, who lives in Boston with her family and needs a 24-hour team of caregivers. Atamian says Natalie is significantly delayed developmentally and has about three to 10 major seizures a month. “We are constantly afraid of her not breathing or dying during a seizure.”
Atamian met Tan in 2015 when Tan was a postdoctoral fellow at Baylor College of Medicine in Houston, conducting research on the CIC gene mutation. While she knows that Tan’s research may not lead to treatment anytime soon, she is grateful for her work.
“To know that there’s a researcher out there who’s completely willing to dedicate her career to events that arise out of this mutation and in a broader sense, to helping children with epilepsy, it’s really a gift.”