For Sucheta Joshi, MD, MS, FAAP, FAES, Medical Director of the Comprehensive Epilepsy Center in the Neurological Institute at Children’s Hospital Los Angeles, one of the most exciting advances in pediatric epilepsy research is how quickly genetic testing has transformed care.
“I have lived through an era in this field,” Dr. Joshi explains. “We went from not knowing why a child has epilepsy, to identifying a genetic cause for the disorder, to developing gene-based interventions for specific types of epilepsy.”
CHLA’s Comprehensive Epilepsy Center is the only Level 4 Pediatric Epilepsy Center in a free-standing children’s hospital in Los Angeles and a leader in pediatric epilepsy care, providing the full range of diagnostics and treatments that enable experts like Dr. Joshi to individualize care to each patient. “For certain forms of epilepsy,” she says, “we can now tell families that we will soon have a drug that will target not only the child’s seizures, but also the root cause.”
Studying genes to create precision epilepsy treatments
Researchers have identified over 1,000 genes linked to epilepsy—a number that continues to increase. This has opened the door to a variety of precision treatment possibilities, which is why CHLA has an on-site clinic for genetic testing.
“Understanding what a gene does and how it might modify brain cell function can direct us toward antiseizure medications that we know will work for that genetically modified epilepsy, or help us to avoid certain drugs which could make seizures worse for someone with that genetic mutation,” Dr. Joshi says. “In addition, clinical trials are now investigating gene therapies, which could help improve the function of a particular gene that is not working properly.”
For example, Dravet syndrome is caused by mutations in the SCN1A gene.
“There are certain antiseizure medications which actually make seizures worse for kids who have this mutation because of the way they impact sodium ion channels in the brain,” she explains. “Conversely, there are medicines that are FDA-approved for treating SCN1A-based disorders. If we identify this mutation in a patient through genetic testing, we can avoid using inappropriate medications and pick these FDA-approved medications sooner in the child’s course of treatment.”
Genetic testing has also led to the development of targeted treatments that don’t involve medication, such as the medical ketogenic diet—a high-fat, moderate-protein, low-carbohydrate diet that can be useful in some genetic forms of epilepsy.
In GLUT1 deficiency syndrome, a patient has trouble transporting glucose from the blood to the brain, starving the brain of its usual fuel and causing a variety of neurological symptoms, including seizures. But with a ketogenic diet, the body breaks fat down into molecules called ketones, which serve as a backup fuel for the brain. “This can have profound effects on seizure reduction,” Dr. Joshi says.
In addition to dietary treatments, she notes that surgical techniques and neuromodulation, or brain stimulation, have made great progress in reducing or eliminating seizures.
Overcoming challenges in care
Among those with epilepsy, about 25% to 30% of individuals have treatment-resistant epilepsy. In some other cases, treatments can reduce the frequency of seizures but cannot eliminate them.
“Getting children to a comprehensive pediatric epilepsy center for genetic testing in a timely fashion is key to treating them effectively,” Dr. Joshi says. “We still don’t have uniform access to genetic testing across the country, and we’ll need that to be able to provide all kids with state-of-the-art diagnostic and therapeutic interventions.”
“At CHLA, we are fortunate to have excellent collaboration between medical genetics experts, neurologists, epilepsy specialists, and our Center for Personalized Medicine,” she explains. “We all work together to provide a treatment tailored to each child we see.”