Like any gene, SCN1A is a blueprint. Specifically, it builds a subcomponent of a sodium channel that ferries ions across cell membranes in the muscles and brain. And in about 85% of kids with Dravet syndrome, whether due to deletion, duplication or disruption to the code, SCN1A can't do its job.
"SCN1A is especially present in interneurons that suppress neural activity," says Kelly Knupp, MD, pediatric neurologist at Children's Hospital Colorado. "And when you have an abnormality in suppressing neurons, the result is seizures."
About Dravet syndrome
For children with Dravet syndrome, those seizures begin in the first year of life and increase in severity — enough to land children in intensive care. Worse, they come with a risk of sudden death. Most research on Dravet syndrome has focused on seizure mitigation, and Dr. Knupp currently serves as site investigator for a national trial of fenfluramine, showing good promise for doing just that.
But Dravet syndrome is a gene mutation, and it impacts many more systems than just the brain. Kids develop endocrine and gastrointestinal problems, as well as problems with walking, behavior and sleep.
"Much like cystic fibrosis, or any other genetic disorder, there's a primary component," says Dr. Knupp. "But your genes have an effect on other organ systems, because your genes are in all of your cells."
Partnering with families
Through a Tier 1 award from the Patient Centered Outcomes Research Institute (PCORI), a relatively new funding model dedicated to exploring treatment outcomes from a quality-of-life perspective, Dr. Knupp is working with the Dravet Syndrome Foundation to determine treatment priorities for parents of children with Dravet syndrome, and, eventually, to develop research projects to address them. And because Children's Colorado is a regional treatment hub for Dravet families, Dr. Knupp talks to a lot of families living with the condition.
"There are so many areas for research, but unless we're partnering with families, we don't know what to tackle first," says Dr. Knupp. "How disruptive are sleep issues? How many kids aren't able to eat regular meals and require supplements? How significant are behavior issues? These are questions we're just starting to ask."