Following treatment, children experienced fewer seizures and demonstrated improved communication and other developmental skills – outcomes not generally possible with typical antiseizure medications.

Researchers at Cook Children’s played a key role in the clinical trials that led to these findings, which were published in a March 2026 article in the New England Journal of Medicine (NEJM). Pediatric epileptologist M. Scott Perry, M.D., head of Neurosciences and director of the Justin Institute at Cook Children’s, co-authored the article and served as the lead investigator for one of the pivotal studies.

Dravet syndrome affects about 20,000 people in the United States. It causes seizures and problems with speech, sleep, development, intellectual abilities and more. About 100-125 patients from across the country come to Fort Worth seeking out Cook Children’s nationally recognized expertise in Dravet syndrome care.

Two initial studies – called MONARCH and ADMIRAL – enrolled 81 patients at multiple sites, including four patients at Cook Children’s. Two extension studies – SWALLOWTAIL and LONGWING – enrolled 75 patients. Dr. Perry served as lead investigator of SWALLOWTAIL.

The primary purpose of the studies was to assess the safety of zorevunersen, a medication administered via spinal tap. Participants received different amounts to help determine an optimal dosage that works safely and effectively.

The results are exciting, Dr. Perry said, because they indicate zorevunersen modifies Dravet syndrome by targeting the root cause. Study participants had fewer seizures and improvement in decision making, social interaction, communication, motor skills and other adaptive behaviors. 

“We have a treatment which at least in early phase studies shows the potential to address the underlying genetic reason for the condition and as a result bring about improvements in the symptoms and frankly change the course of the condition for the patient, which is a considerable advancement over what we currently have available,” Dr. Perry said. 

Adverse side effects were mostly mild or moderate, including elevated protein in the cerebrospinal fluid and pain after the spinal tap procedure.

Understanding Dravet

Most people diagnosed with Dravet syndrome have a mutation in the SCN1A gene that disrupts the production of normally functioning sodium channel proteins in the brain. The sodium channel is essential for neurons to fire appropriately. Seizures occur when the electrical flow misfires.

Antiseizure medication is currently the standard of care. But antiseizure medications don’t always control the seizures. And even when the frequency of seizures drops off, the patient’s cognitive delays and other symptoms don’t necessarily improve. 

“Dravet is a condition called a developmental and epileptic encephalopathy, which means the seizures themselves cause problems, but the underlying reasons for the seizures also cause problems,” Dr. Perry said. “This drug aims to address that by treating the actual genetic abnormality. And when you correct the gene that causes the problem, now you can improve seizures and the nonseizure symptoms that come with it.”

While one copy of the gene produces good proteins, Dr. Perry explained, the mutated version found in Dravet makes proteins that don’t function effectively. Zorevunersen is a precision medicine that capitalizes on the healthy copy of SCN1A.

How does it work? Ribosomes are the part of the cells that read messenger RNA (mRNA), which Dr. Perry described as the recipe that forms the sodium channel. Zorevunersen prompts the ribosomes to skip over the portion of mRNA that discards both healthy and unhealthy copies of the gene. No longer discarded, more healthy copies are available to create more functioning sodium channel proteins.  

Methods and Findings

Patients with Dravet syndrome from ages 2-18 years participated in the MONARCH, ADMIRAL, SWALLOWTAIL and LONGWING trials beginning in June 2020. Eighty-one percent of participants were taking three or more antiseizure medications prior to their first dose of zorevunersen.

The main objective was evaluating the safety of the trial therapy. Patients received one or more doses ranging from 10 milligrams to 70 mg. Data showed a reduction in seizures compared to the patients’ baseline numbers.  

“What we determine from these studies is that initial doses of 70 mg performed better than any of the lower doses,” Dr. Perry said. “People who got multiple doses of 70 mg did better than people who got single doses. People who got two doses of 70 mg did similarly to people who got three. That’s why we’ve chosen two 70 mg doses as the loading dose for the ongoing phase 3 clinical trial.” 

Participants in the extension studies followed up by receiving doses up to 45 mg every four months. At that level, they continued to maintain the similar reduction in seizures, he said.

Changes in adaptive behaviors and quality of life were measured by various scales based on impressions from clinicians and caregivers. Improvements were reported across the board. 

Biotechnology company Stoke Therapeutics, Inc. opened the next phase of the trial, called EMPEROR, in August 2025. Participants will receive either zorevunersen or no treatment in four spinal taps over a 52-week period.

Dr. Perry said inclusion in the NEJM article shows Cook Children’s is making a significant contribution to a big advancement in Dravet syndrome care. By joining clinical trials, research sites help find solutions and hope for patients with complex conditions.

“Cook Children’s does meaningful research. This is clinical trial work developing novel new therapies for devastating diseases,” he said. “Cook Children’s played a key role in the development of this treatment, and the NEJM is an incredibly prestigious journal. It’s a big deal for Cook Children’s to be a major contributor to such a huge contribution to science.”

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Running around too much or getting too hot used to trigger seizures several times a week for 8-year-old Sebastian Ruiz.

But since he started new investigational treatment through a clinical study at Cook Children’s, the seizures happen less often -- once or twice a month – and don’t last as long, Sebastian’s mom said.

Sebastian is one of about 20,000 people in the United States with a rare form of epilepsy called Dravet syndrome. Along with seizures, the disorder also leads to problems with speech, sleep, development and intellectual abilities among other issues. Sebastian was diagnosed with Dravet syndrome at 15 months old.

Juan and Rainey Ruiz make the two-hour drive from their home in Rosebud, Texas, to Cook Children’s Medical Center in Fort Worth so that their son can receive a new treatment still in the trial stage. That medication, called zorevunersen, works to offset the genetic malfunction that causes Dravet syndrome.   

Rainey Ruiz said Sebastian used to have seizures that sometimes lasted from 30 minutes to an hour. Other medications weren’t helping. Now he receives a dose of zorevunersen every four months via spinal tap as part of the SWALLOWTAIL study. Rainey is grateful Sebastian has the chance to try an innovative therapy.

“When you’re a mom, you’re just desperate for anything and hope you’re doing the right thing,” she said. “It’s hard for me to be content with where we are and not try for something better for him.”

The U.S. Food and Drug Administration in December 2024 granted the medicine a breakthrough therapy designation as a potential disease-modifying treatment for Dravet syndrome. In Dravet syndrome, one of the two copies of the SCN1a gene has a variant, or change that impairs the genes ability to make a normally functioning sodium channel. The sodium channel is essential for the brain's neurons to fire appropriately. Zorevunersen is designed to capitalize on the healthy copy of SCN1a, helping it produce more functional sodium channel proteins in the brain, addressing the disorder’s root cause rather than just treating its symptoms.

Biotechnology company Stoke Therapeutics, Inc. opened a third phase of the trial, called EMPEROR, in August 2025. M. Scott Perry, M.D., epileptologist and head of the Justin Institute at Cook Children’s, serves as lead investigator at Cook Children’s. The trial across approximately 70 sites involves 170 children and teens who have the SCN1A gene variant responsible for Dravet syndrome. The goal? To assess the medication’s safety and its impact on seizures, communication and other areas.

Patients enrolled in the EMPEROR trial undergo four spinal taps over 52 weeks, the first two 8 weeks apart and each additional procedure every 16 weeks. Patients will either get zorevunersen or no treatment during the 52-week period. The trial’s first patient from Cook Children’s received their initial dose in September 2025. 

Dr. Perry said patients in SWALLOWTAIL and other earlier phases experienced fewer seizures, less severe seizures and improved ability to communicate and interact, as well as improvements in motor skills.  

“The disease-modifying therapy is trying to correct the underlying cause,” Dr. Perry said. “And if you can correct the underlying cause or at least lessen the underlying cause’s impact, then you can have improvement across multiple manifestations of the disease.”

How It Works

Most people with Dravet syndrome have a mutation in the SCN1A gene that disrupts the production of normally functioning sodium channel proteins in the brain, causing abnormal electrical flow that leads to seizures. While one copy of their gene is producing good proteins, Dr. Perry explained, the mutated version is producing proteins that don’t work effectively. 

Ribosomes are the part of the cells that read messenger RNA (mRNA), which Dr. Perry described as the recipe that makes up the sodium channel. Zorevunersen prompts the ribosomes to skip over and not read the portion of the mRNA that destroys both healthy and unhealthy copies. Because they’re not being discarded anymore – a natural process to limit overproduction of proteins -- more healthy copies are available. As a result, more functioning sodium channel proteins can be created.  

“You end up basically getting almost 100% of the healthy version through to make up for what you’re losing on the unhealthy side,” Dr. Perry said.

Cook Children’s treats about 100-125 Dravet syndrome patients from across the country. As a recognized leader in epilepsy care and research, Cook Children’s was the initial site Stoke Therapeutics visited ahead of the EMPEROR trial. Cook Children’s Neuropsychology, Neurodiagnostics, Anesthesiology, Radiology and MRI departments are involved as well.

“I think it underscores what is possible at Cook Children’s from a research standpoint,” Dr. Perry said. “That is not a simple trial. It’s quite complex in its design. Cook Children’s was selected to participate because we can do it well. We have a track record of doing it well.”

Current options in doctors’ toolkits focus on treating the seizures, he said. Other symptoms, such as speech, still present problems. Zorevunersen gives doctors hope that precision medicine will change the genetic factors behind Dravet syndrome so that patients see improvement across the board.

Spotlight on Sebastian

Sebastian had his first seizure at 4 months old and the next one three months later. They happened more frequently after that, and sometimes he had to be intubated at the hospital during a seizure. He started coming to Cook Children’s at age 2 years when the Ruiz family sought out a neurologist who specialized in Dravet syndrome. 

“Dr. Perry is the top. He’s amazing,” Rainey said. 

Sebastian had been enrolled in several clinical trials prior to SWALLOWTAIL. Now a third-grader, Sebastian has limited ability in speech, but he recently started recognizing letters of the alphabet. He loves basketball, school and his four siblings. Running a fever, overheating or overstimulation can still bring on seizures -- but not as often since he started the zorevunersen therapy, his mom said.

Participating in clinical trials can be long and hard, and there’s no guarantee the medication will benefit your child, Rainey pointed out. But trials provide hope for better outcomes for patients in the future. She encouraged parents of Dravet syndrome patients to consider enrolling if that’s an option for them.  

“It’s just hard for me to stand by and not try to do something,” she said. “Even if it helps other kids, it’s still a win-win. You can change lives in other ways.”

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 Colton was diagnosed with Dravet Syndrome just before he turned one.

 “We didn’t know anything about Dravet,” said Mindi Ragsdale, Colton’s mom.

 As a newborn, Colton passed all screenings, but at just a few months old, he began having seizures lasting up to 20 minutes. The infant was airlifted from his hometown of Hobbs, New Mexico, to Lubbock, where he was diagnosed with epilepsy.

Driven by a mother's intuition, Mindi began researching what was causing the seizures and learned about Dravet syndrome, a rare disease. Dravet is estimated to occur in 1 in 15000. Her pediatrician recommended Cook Children's Medical Center in Fort Worth, one of the largest clinics in the United States specializing in Dravet Syndrome.

 Scott Perry, M.D., head of Neurosciences at the Jane and John Justin Institute for Mind Health at Cook Children’s, explains that Dravet syndrome typically begins in an otherwise healthy child around 6 months old with the onset of seizures.

 “When we went in, it all just fell right into place because Dr. Perry had already treated kiddos with Dravet. It was like it was all meant to be,” recalls Mindi.

 Dr. Perry listened to Mindi and did genetic testing. Dravet syndrome is most often caused by a variant in a gene called SCN1A.

 Colton was admitted to the hospital, where Dr. Perry monitored his seizures. It was Dr. Perry’s demeanor and knowledge that helped put Mindi at ease.

 “He was just so down to earth and just so knowledgeable,” said Mindi.

 Dr. Perry says listening to parents is imperative when trying to find a diagnosis.

 “Every time you see them, it is an opportunity to hear the story from the very beginning to where you are now,” said Dr. Perry. “Sometimes you have to step back and see the whole story.”

 For years, the family traveled from New Mexico to Fort Worth for medical appointments. In 2023, the Ragsdales moved to Fort Worth. They say it changed the family’s life.

 “It’s like we didn’t have to live in a bubble for the first time in five to six years,” said Mindi.

 Going to a new place could trigger a seizure, making the family cautious about outings. Now, just 20 minutes from Cook Children’s Medical Center – Fort Worth, the family has been able to explore new places together.

 “We've learned through the therapies at the school how to help him cope,” explained Mindi.

 At 11 years old, Colton began attending Jo Kelly full-time, a significant milestone for him.

 Jo Kelly School

 Colton begins each day at Jo Kelly by checking his communication schedule. Each picture card visually guides him through his school routine, from washing his hands to reading.

 “I feel my job here is to not only make the students' life better, but to make their home life better,” said Baldacci.

 That impact is already being felt. Colton, who previously communicated primarily through screaming and yelling, now uses an eye-gaze tablet to express himself.

 “If he wants to do more of something, then he can look at that and he can do more of it,” said Mindi.

 Baldacci adds that Colton recently met a communication milestone: He was able to tell her to stop an activity to move on to another.

 “For the first time, he finished and touched [the card] without pushing the whole thing,” said Baldacci.

 Connecting families to resources

 Mindi credits Cook Children's with being a bridge to local resources. She learned about Jo Kelly from another mom while waiting for Colton's appointment.

 “I was asking her about her wheelchair because Colton had a regular wheelchair,” said Mindi.

The wheelchair was provided through Jo Kelly, which led Mindi to begin the enrollment process. The school, which focuses on medically fragile children from ages 3 to 22, has two teachers for three students, a nurse, and three medical assistants on campus. A specialized cafeteria on campus focuses on preparing food based on students' needs.

 “His syndrome is so complex it was important to me to have somebody medically there at all times,” said Mindi.

 It was the reassurance she needed, and Dr. Perry encouraged her to enroll Colton.

 "It's not just my job to help pick the right medicines and treatments, but when they need these services, they need somebody generally to advocate for why the service is a value to them and how it's going to help them," Dr. Perry said.

 The Ragsdales say their move has been a night-and-day change. Enjoying making memories as a family, Mindi shared that Colton had his first photo with Santa, an opportunity the school set up for the students.

 It was a small moment that meant a lot.

 “When we would have been doing that type of stuff, we were fighting his seizures and all of his medical issues,” shared Mindi.

Students have a routine that includes reading, circle time, time on the handicap-accessible playground, cooking class, and time in the sensory room.

"It's really neat that Jo Kelly tries to make it as normal as possible," Mindi said. "Even though their lives are so far from normal, they still try to incorporate all that."