Using Pharmacogenomics to Find the Right Therapy for Pediatric Epilepsy

Cannabidiol, commonly referred to as CBD, is a non-psychoactive compound from the cannabis plant. Epidiolex—the only FDA-approved CBD medication—is used when other anti-seizure drugs aren’t effective for children with pediatric epilepsy. But dosing is complicated, and what works for one child may not work for another.

For Katelin Brito, a member of TCOP’s research track, the research began with a personal connection. Years ago, her brother-in-law was diagnosed with a Lennox Gastaut Syndrome, a severe form of pediatric epilepsy. Later, by coincidence, he was prescribed Epidiolex. The experience wasn’t a positive one. “It was a trial run,” she said. “Within a month his seizures got worse, and he was actually experiencing some side effects, including insomnia.” That outcome made her think harder about dosing. “CBD has to be dosed very specifically to each person,” she said.

Genetic Analysis in the Lab Helps Clarify Proper Dosage for Pediatric Epilepsy Treatment

Over the past year, Brito has been working in Dr. Zvi Loewy’s lab, where she received twelve de-identified DNA samples from the Coriell Institute for Medical Research. She used pharmacogenomic assays targeting two major metabolic enzymes—CYP2C9 and CYP2C19—to determine whether each patient sample represented a slow, normal, rapid, or ultra-rapid metabolizer of CBD. Understanding those differences, she said, can directly influence treatment. “Do we decrease or increase, or not give at all? Every person is unique regarding the treatment,” Brito explained. “If a person has an ultra-rapid metabolization, the dosage could lead to toxicity.”

She added that genetic testing might have helped her family member. “If he were to have gotten this genetic testing, the doctor could have seen whether CBD would work for him before he had started it.”

Helping to Inform Parents on Potential Clinical Benefits of CBD

Brito’s research project also includes a survey questionnaire for parents and guardians of children with epilepsy. She wants to understand how families feel about CBD treatment. “When people hear CBD, they don’t know anything informative about it,” she said. “They might think it’s referring to THC (Delta-9-tetrahydrocannabinol), the psychoactive compound of marijuana, which it’s not.” She hopes the results will give clinicians a clearer picture of what families need. “I want to get more insight for these children,” she said. “The parents or guardians are going to be the ones communicating with the doctor.”

How Brito Found Her Calling in Pharmacy Research

Before coming to Touro, Brito studied biology with a concentration in organismal physiology and minored in psychology at Drexel University in Philadelphia. She initially planned on going into dentistry. “At the last minute, I asked myself: ‘Do I see myself doing this in twenty years?’ I realized pharmacy had more career options for me.”

Brito will present her findings at the ASHP Midyear conference in December. She hopes that pharmacogenomics will eventually help clinicians avoid the trial-and-error stage of epilepsy treatment—and get children the right therapy or dose of CBD from the start.