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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Bridging Innovation and Patient Care

Backed by over 20 years of translational research experience and with 100+ peer-reviewed research investigation articles under his belt, Dr. Papadelis brings a wealth of scientific expertise to this partnership, all driven by compassion for people. 

“What I like to see with my research is how to help children,” Dr. Papadelis said. “That's why I like what's called translational research. It's not science for the sake of science. It's science for the sake of applying the knowledge to help somebody.” 

Both organizations provide critical assets for translational research, which is the bridge connecting basic discoveries to the application of those discoveries within patient care. 

“UTA has been active in translational research for a long time, but we want to expand in big ways,” Dr. Weidanz said. “I think Dr. Papadelis and this growing partnership with Cook Children’s is really setting all of that in motion. It’s really unique that we can bring the best of both worlds together so that we both excel in translational medicine. It’s a win for all of us, and most importantly, for patients.” 

With its brain-trust of academic researchers, including doctoral and postdoctoral candidates, as well as leading-edge laboratories and technology, UTA provides the infrastructure for imagination-driven discovery that could lead to breakthroughs in treating rare and complex neurologic conditions in children. 

Cook Children’s diverse patient population offers UTA researchers an expanded pool of potential study participants. In addition, the health system’s vast network of clinical experts, who understand the unique needs and challenges of pediatric health care, can apply and evaluate research findings in real time within their care settings. 

“Our department is a support system for this work,” said Luke Hamilton, Cook Children’s director of Clinical and Translational Research. “Our scientists have expertise in translating data produced from clinical encounters, aggregating, and analyzing for findings to create a new evidence base that can be fed back to our clinicians and improve clinical care."

A Ripple Effect

Along with enhancing Cook Children’s ability to deliver evidence-based innovation in patient care, this collaboration boosts both organizations’ ability to attract competitive federal funding, postdoctoral talent and joint appointments, which increases their visibility in academic publishing and conference networks. 

The local economy could score big, too. 

“We shouldn't overlook economic development and the impact we can have on growing our community,” Dr. Weidanz said. “I think these collaborations, starting with Dr. Papadelis and looking forward to what comes next, could eventually lead to the commercialization of some of these new findings, and that translates to jobs. Of course, we’ll never lose sight of the patient, but these partnerships really help the community flourish."

From Ancient Cities to the Western Frontier

Born in Athens, Greece, and raised in Thessaloniki, Dr. Papadelis parlayed an electrical engineering diploma from Aristotle University into a career studying the electrical pathways of the pediatric brain, taking special interest in epilepsy and movement disorders such as cerebral palsy. 

“I found that engineers like objects, but they don't like communicating with people,” Dr. Papadelis said. “I'm a very extravagant personality. I like to connect with people, and I talk a lot, so I realized I didn't belong there. But the engineering school gave me knowledge of how to use engineering skills in health care to help physicians. That’s when I went for a master’s and Ph.D. in biomedical engineering. I found my spot there and realized there is so much technology and tools that we can use to help physicians, and this is what I found fascinating.” 

In his prestigious career, Dr. Papadelis has lived and worked in five cities throughout four different countries across three continents. At the RIKEN Brain Science Institute in Japan, he honed his skills in the neuroimaging technique known as magnetoencephalography (MEG)—the fastest brain imaging tool available, allowing doctors to see brain activity in real time. In Trento, Italy, Dr. Papadelis marveled at his daily view of the Italian Alps while completing a post-doctoral fellowship at the Center for Mind/Brain Sciences at the University of Trento. 

In 2011, the neuroscientist made his way across the pond for his first faculty appointment—a professorship teaching neurology at Harvard Medical School. He also joined the research staff of Boston Children’s Hospital, where he led the development of its clinical MEG laboratories and programs. 

Cook Children’s invited Dr. Papadelis to join the health system in 2019. His heart for connection made him the perfect fit for a health system whose promise to do everything for the child is fueled by kindness, collaboration and imagination. The prospect of warmer weather made the offer all the more attractive. 

“I was looking for a change in my career, and I decided to give it a try,” Dr. Papadelis said. “I moved down here with my family, and we love it. We felt really welcome. Being Greek, I feel like I belong in the south because I like the weather.” 

Dr. Papadelis was first named Cook Children’s founding director of Research within its Neurosciences program. In September 2024, he became the assistant vice president of Research at the newly opened Jane and John Justin Institute for Mind Health at Cook Children’s. The Cook Children’s team he leads includes several UTA faculty members, postdoctoral researchers, alumna and research assistants, as well as a host of UTA doctoral students. 

Since arriving in North Texas, Dr. Papadelis has led Cook Children’s to new heights with several “firsts” for the health system. These include Cook Children’s receiving its first research grant from the National Institutes of Health, securing its first patent, and achieving its first fully approved Institutional Review Board (IRB) protocol for using Transcranial Magnetic Stimulation in conditions like cerebral palsy. 

While his research covers a broad range of studies in neuroscience, clinical neurophysiology and biomedical engineering, Dr. Papadelis’ main goal is to develop a novel epilepsy biomarker that will help children with drug-resistant epilepsy become seizure-free after resective neurosurgery, and he’s well on his way. Under his leadership, Cook Children’s Neurosciences research team has uncovered several new signs for identifying the epileptogenic zone with high precision, and developed new AI tools for predicting surgical outcomes in children with drug-resistant epilepsy. These discoveries and prediction tools help guide physicians in their treatment, improve the accuracy of surgical interventions, and give new hope to patients with uncontrolled seizures. 

“Cook Children’s is not just a hospital that takes care of the children in the region,” Dr. Papadelis said. “We develop here, and we perform very innovative research that has been recognized nationally and internationally by the scientific community.” 

Shortly after joining Cook Children’s, Dr. Papadelis also joined UTA’s faculty as a professor of Bioengineering. From that relationship grew the framework for the Pediatric Brain Health and Neurosciences Center partnership. In addition to his Cook Children’s team, Dr. Papadelis oversees a 16-member research team at UTA, while also mentoring several doctoral and postdoctoral candidates. 

“Dr. Papadelis is an incredibly passionate, creative and curious scientist with an eye on delivering his research findings to the patient,” Dr. Weidanz said. “He laid the groundwork for what’s to come, and that is a very strong partnership between UTA and Cook Children’s.” 
 

She and her husband, Zach Beavers, spoke with numerous hospitals, but none would take them. Most places were either not willing or not equipped to handle the heart defect that had been detected in their unborn daughter.

While still in the womb, Anna Claire was diagnosed with a rare heart condition in which the left side of the heart is too small to pump blood. To make things more complicated, she also had a genetic condition that stilted her growth. Two months before Anna Claire’s due date in April, the Beavers’ found out their home hospital in Georgia was not willing to operate on her due to the high risks.

With less than a month to go, the Beavers found a ray of hope when their doctor heard about a hospital in Texas that had unusually positive results treating Anna Claire’s condition. There seemed to be one place that would help them: Cook Children’s Medical Center – Fort Worth. 

One of the first things Cardiologist Kevin Wilkes, M.D. learned about Cook Children’s was that the hospital doesn’t shy away from taking care of the most medically complex children. As a pediatric and fetal cardiologist, Wilkes also quickly learned—and is part of the reason—that Cook Children’s excels at treating those children.

In 2024, Dr. Wilkes noticed one area in particular where Cook Children’s seemed to achieve better patient outcomes than other hospitals: a rare but life-threatening combination of Hypoplastic Left Heart Syndrome (HLHS) and Turner Syndrome. In HLHS, the left side of the heart does not develop properly and cannot pump blood to the body. In Turner Syndrome, the X chromosome is missing or partially missing. In very rare cases, babies -- like Anna Claire -- can have both.

Through the Pediatric Research Program, a partnership between UNT Health Fort Worth and Cook Children’s, third-year medical student Anisha Saripalli started to look into the numbers. Over the summer of 2024, she, along with Research Scientists Chris Tsao and Fadeke Ogunyankin, dug through electronic case records in Cook Children’s basement. The results were compelling.

Compared to other hospitals, Cook Children’s outcomes for babies with Turner Syndrome and HLHS are some of the best in the nation, far exceeding the mortality rate of other centers. On average, between 80 and 90% of babies with both conditions die across the country after their first surgery. In fact, the prognosis at many hospitals is so poor for those patients that many places won’t even attempt to perform surgery on a baby with both conditions. However, at Cook Children’s, 100% of babies survived their first surgery.

“That's pretty solid to recommend that these patients go through the surgery, because we're increasing their chance of having a good life. And we're not just saying, ‘oh, well, you're incurable, untreatable,’” Saripalli said.

In short, Cook Children’s gives these babies a chance.

And hundreds of miles away, one family was asking for just that.

In February 2025, the same month that Saripalli’s research was presented at a cardiology conference, the Beavers found out that Anna Claire had both HLHS and Turner Syndrome.

Their birth plans suddenly vanished; the Atlanta hospital where Sarah Ellen planned to deliver said it did not have the ability to treat Anna Claire’s condition.

Because the left side of Anna Claire’s heart could not pump blood, the right side of her heart would need to become the pumping chamber for the rest of the body. But few hospitals are able or willing to perform the surgery on babies with Turner Syndrome due to the added complications.

Anna Claire would need three heart surgeries, the first of which -- called the Norwood surgery – would have to be done within three days of her birth. The Beavers contacted several major heart centers, but they all said they could not take Anna Claire.

“We were just hoping someone would say yes. Because statistics really were not super favorable, and so we were really prepared for the worst,” Sarah Ellen said. “But we were just hoping for a chance.”

At the end of February, Dr. Wilkes presented Saripalli’s research at a Cardiology Conference in Florida. She and the research team found that between 2013 and 2024, Cook Children’s saw six babies with HLHS and Turner Syndrome. In contrast to the high mortality at other hospitals, at Cook Children’s, five of the babies (83%) are alive. 

Coincidentally, the Beavers’ cardiologist happened to attend the presentation. He immediately thought of his patients back in Georgia.

“On Friday afternoon, our home cardiologist called us and was like, ‘hey, there's someone with really good statistics,” Sarah Ellen said. “And that probably got us through the weekend, because we already had gotten two ‘nos’ from hospitals. And we were like, ‘What are we gonna do?’ We don't have time.”

That Monday, the Beavers scheduled a phone call with Dr. Wilkes and Vincent Tam, M.D., the Medical Director of Cook Children's Cardiothoracic Surgery. Dr. Tam walked them through the procedures he would perform on Anna Claire. While other hospitals would not consider taking on Anna Claire’s condition, Dr. Tam seemed undaunted.

“(Tam) never balked at any of it,” Zach said. “He never thought that it was a challenge or any concern, and just made it seem like he's just gonna do the same thing that he always does, and it was gonna be great.”

The Beavers packed the biggest suitcases they had and, leaving behind their home hospital and friends and family, headed to Texas.

On March 25, the Beavers stepped into Cook Children’s for the first time.

“We walked the halls receiving a quick tour and then we had the opportunity to meet with Dr. Tam, Anna Claire’s surgeon,” Sarah Ellen wrote that day on the family’s CaringBridge blog, which provided updates on Anna Claire. “After over an hour with him, we were more at peace believing that the Lord intended for us to be here all along.”

Leading up to Anna Claire’s birth -- and her open-heart surgery – Dr. Tam, Dr. Wilkes and other Cook Children’s staff did everything they could to make the Beavers comfortable and confident. Dr. Tam explained the surgery to them again and it was clear to the Beavers that he had studied and perfected the procedure.

But there was still a risk. Saripalli said there is not much research on babies with both HLHS and Turner Syndrome because the condition is so rare.

But Dr. Tam and Dr. Wilkes were confident. Cook Children’s has such good outcomes, they said, because of the infrastructure and support built into every layer of the medical center.

“I've been here at Cook Children’s for more than 20 years, and we have gradually built a team to the point where we really have excellent people working in all of the teams involved,” Dr. Tam said. “Including nursing staff, respiratory therapy, the technicians that do the ultrasound for the Echo, all of our cardiologists, the ICU doctors, the anesthesiologist doctors, the nurses that help with anesthesia. And my whole operating room team. I mean it's a huge team effort.”

On April 3, that medical team assembled to welcome Anna Claire to the world.

Anna Claire was born right on time, at 4:56 a.m. on her due date at a nearby hospital before being transferred to Cook Children’s and Dr. Tam knew he had to move quickly so that the right side of her heart didn’t overwork itself. The next day, Anna Claire had her first open-heart surgery.

The group effort paid off; Anna Claire’s first surgery was a success. The team successfully began the process of reworking the right ventricle to support the rest of her circulation.

The following week brought another scary moment when blood and fluid started to build up around Anna Claire’s tiny heart and the medical team determined they needed to open her back up. Fortunately, Dr. Tam and the team found the source of the bleeding and stopped it immediately.

The next weeks brought other challenges and still more members onto Anna Claire’s medical team. Her feeding, oxygen levels, sleep patterns and every internal system were constantly monitored. The next five weeks, Zach said, felt like months.

“Yeah, there were days it was just… you kind of went to bed like, ‘man, this was a lot,’ and you woke up knowing ‘we're doing it again today,’” Sarah Ellen said.

But they also found support at Cook Children’s.

“In these days, this place has held us,” Sarah Ellen wrote at the time on her blog. “Strangers have become best friends and family. Nurses and doctors have become dear friends. Staff members have learned our family’s story. The doors we walked in on March 25 have become a place we will forever call home.”

Anna Claire was able to temporarily leave the hospital on May 30 and stay at the Beavers’ temporary home that a local DFW family offered them. On July 24, she had her second open- heart surgery. While anxiety-inducing for the Beavers, the surgery went well, and Anna Claire made the monumental milestone of moving from the ICU to the less intensive Cardiac Step Down Unit.

Exactly five months after the Beavers arrived -- unsure of how long they would be away from home and uncertain about their daughter’s future -- the family of three left Fort Worth to head back home to Georgia.

Leaving was emotional for many reasons. They were excited to return to their home, family and, most importantly, their Georgia Bulldogs (Anna Claire had a jersey waiting for her at home). But they had to say goodbye to the dozens of people at Cook Children’s who made one of the most challenging times of their lives into something bearable. On Aug. 8, they visited the Cardiology Unit with Anna Claire, who wore a jumper adorned with blue flowers and a white bow. The staff excitedly gathered around her, commenting on how strong she looked and how well she drank from her bottle.

Two of Anna Claire’s nurses with the Home Monitoring Unit, Emma Hughes and Mariah Trammel, marveled at how she had exceeded everyone’s expectations.

“Just in general, having her heart diagnosis is really challenging and she has a genetic component on top of that, which adds to the complexity,” Mariah Trammel, Heart Center Discharge Coordinator, Cardiology-Administration, said. “So we were one of the only institutions that were willing to take her on and do her surgery. And she has done incredibly well.”

Before leaving Fort Worth, they also met Saripalli for the first time. For Saripalli, meeting the family brought home the fact that her research, and the decades of work it's based on, has real, life-saving implications. Saripalli’s project highlighted how Cook Children’s has created a collaboration between research and clinical medicine that leads to immediate impact. Medical research can take years to trickle down to actual patients. Cook Children’s partnerships with universities like UNT Health Fort Worth means solutions can be rapidly translated to real results.

Saripalli, Dr. Tam and Dr. Wilkes hope the Beavers’ story and Saripalli’s research provide a similar ray of hope for others.

“This research at Cook Children's was a game changer,” Dr. Wilkes said. “And I think you see that in how quickly it affected the family. By getting that information out there nationally at a conference within a week, we were able to change the outcome of a family. I hope in the future we can change the outcome of many more families undergoing this type of heart surgery.”

Anna Claire is now seven months old and continues to thrive in Georgia.

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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Their findings were published in March 2025 in the top-tier scientific journal Nature Portfolio Journal Digital Medicine. The article explains how the research team designed and trained a machine-learning tool to specifically locate the seizure starting point in children and teenagers.

During their two-year study, the researchers came up with an automated system that works by analyzing recordings of electrical activity in the brain. The researchers entered the data into the framework, and the system learned to identify where the drug-resistant seizures started.

“The system provides as an output to the epileptologists and neurosurgeons the brain area to resect in order for the patient to become seizure free,” said Christos Papadelis, Ph.D., Assistant Vice President of Neuroscience Research at the Jane and John Justin Institute for Mind Health at Cook Children’s Health Care System.

Dr. Papadelis teamed up with his postdoctoral research fellow Hmayag Partamian, Ph.D., to come up with the project’s concept and experimental design. Dr. Partamian developed the mathematical formulas and codes. The work took place in labs at Cook Children’s Medical Center in Fort Worth and at the University of Texas at Arlington, where Dr. Papadelis serves as Professor of Research in Bioengineering and Director of the Pediatric Brain Health and Neurosciences Center.  

The study utilized data from 43 children with drug-resistant epilepsy who underwent resective surgery. The goal of resective surgery is to stop seizures from occurring by removing the brain tissue where the seizures originate.  

Dr. Papadelis said the new AI-based tool could help improve the outcome of those surgeries by precisely defining which tissue to remove, giving those patients hope for a seizure-free future.

Where Seizures Begin

Nearly 500,000 children nationwide live with the chronic disorder of epilepsy. They suffer from seizures, which are misfiring of electrical activity in the brain. Someone experiencing a seizure might have a blank stare, muscle spasms, or loss of consciousness. Medications control seizures in about 70% of epilepsy patients. The others have what’s called drug-resistant epilepsy. 

The AI tool created by Dr. Papadelis and his team requires just five minutes of recorded brain electrical activity to determine the area of seizure origin. This presents a significant advantage compared to conventional methods that typically require recording the brain activity for several days -- or even weeks -- in order to capture a seizure.

The tool then transforms the electrophysiological data into color-coded maps of brain activity across time and corresponding these maps into active epileptic regions in the brain. Researchers trained the AI tool to automatically discriminate epileptic from healthy brain regions in these maps. Surgical resection of the epileptic regions in these brain maps can predict a good prognosis for the patient.

Dr. Papadelis pointed out important features of the automated process:

• Less chance for human error from manual interpretation of the data
• Reduced costs, time and risks from the presurgical evaluation process

“We have developed an AI, patient-specific method that automatically identifies the brain area that generates seizures in patients with drug-resistant epilepsy. This method requires little to no input from clinicians,” Dr. Papadelis said. “Our method eliminates the need for manual data inspection, reduces prolonged monitoring and enhances surgical planning.”

The study is in collaboration with Boston Children’s Hospital and is funded by a grant from the National Institute of Neurological Disorders and Stroke.

Dr. Papadelis plans to seek extra funding for the study’s next phase: applying the tool prospectively to patients who are candidates for surgical intervention at Cook Children’s.

Dr. Papadelis believes that the findings of this study represent a significant step toward improved surgical procedures for drug-resistant epilepsy.

“Such a framework would be particularly useful to epilepsy centers that lack the multidisciplinary expertise to delineate accurately and precisely the epileptogenic brain regions in complex cases,” the article states.  

Dr. Papadelis credited the dedication of all the researchers, and in particular he highlighted Dr. Partamian’s talent for scripting. The study shows direct benefits that align with the Cook Children’s Promise to improve the well-being of every child in our care and communities, he said.

“This is one of the moments that makes you feel really proud of the work that you have accomplished together with your team,” he said. “We keep our Promise to do our best for improving the lives of children suffering from devastating neurological disorders.” 

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Cook Children’s Neuroscience Research Center, led by Christos Papadelis, PhD, is the recipient of a $50,000 research grant funded by the National Institutes of Health (NIH) through the National Pediatric Rehabilitation Resource Center, also known as CPROGRESS, for a study mapping the brain’s response to robotic-assisted rehabilitation in children with unilateral cerebral palsy.

“We are one of very few centers in the United States mapping changes in the brain as a result of robotic rehabilitation,” Dr. Papadelis said. “It’s not the rehabilitation by itself or the robotic system by itself, but it's the fact that we try to map the brain’s plasticity or what type of plasticity takes place in the brains of these kids in response to the rehabilitation.”    

Cerebral palsy is one of the most common childhood disorders in the United States. About one in every 345 children in the country have some form of the neurological disorder, which affects movement and muscle coordination. The condition can impact the lower or upper extremities, all four limbs or one side of the body. In any case, physical rehabilitation is crucial to maximizing movement and muscle control.

For children with unilateral cerebral palsy, meaning one side of the body is affected, conventional rehabilitation utilizes constraint-induced movement therapy in which the dominant, unaffected limb is immobilized in order to force the paralytic limb to do all of the work. While effective, children aren’t always cooperative with wearing constraint devices and performing this type of repetitive, or what they might call boring, therapy. 

But kids do like video games. As digital natives, they have never known a smart device they couldn’t navigate. For this reason, robotic therapy is emerging as an important rehabilitation tool for children. The digital nature of the bot captures their attention and speaks a language they understand. 

While researchers know robot-assisted rehabilitation has its benefits, there is a lot they still do not know about the application of this type of therapy in the pediatric population.

“There's not much research on how robotics help children with cerebral palsy,” Dr. Papadelis said. “We don’t yet have a gold standard on how much treatment, how many days and how intense it should be in order to have successful outcomes. We want the brain to reorganize based on the rehabilitation, but can this kind of mapping be maladaptive and go in a direction we don’t want it to go?”

Thanks to the NIH grant, Cook Children’s Neuroscience Research Center is studying the use of robot-assisted rehabilitation for children with unilateral cerebral palsy in order to address these uncertainties and establish best practices. 

The robot used is akin to a video gaming system. Using the fingers and hand of the impacted limb, patients manipulate a type of sensor-based robotic joystick while playing a video game generated by the robot’s computer system. The system measures functions such as range of motion, spasticity and strength in order to tailor the interactive video games to the patient and increase engagement. It also uses vibrations to stimulate the patient’s motor sensories.  

“There's a hypothesis that the more information we provide to the somatosensory system in the brain, the better the motor responses,” Dr. Papadelis explained.

While interacting with the robot, patients also undergo an electroencephalography (EEG) study where dozens of electrodes are placed on the scalp to measure the electrical activity of the brain. 

“Using this tool, we are able to map changes in the brain as a result of this rehabilitation. It tells us if the parameters of the treatment are sufficient, or if we need more intense treatment, less intense treatment and whether this type of treatment is beneficial for one child or for all kids,” Dr. Papadelis said. “Kids with cerebral palsy all have different underlying etiologies. For example, some kids have cerebral palsy as a result of stroke. Some as a result of infection or hemorrhage. Because cerebral palsy is an umbrella term, we're trying to understand if this treatment is beneficial and for which group of patients. And, if it's beneficial for this group of patients, how much we should provide them in terms of treatment length.”

Sadra Shahdadian, PhD, a postdoctoral research fellow under Dr. Papadelis’ supervision, serves as co-principal investigator for the study. Drs. Papadelis and Shahdadian hope that at the completion of this one-year grant cycle the research team will have collected enough preliminary data to support their hypothesis and better define the use of robot-assisted rehabilitation in children with cerebral palsy. They also hope their work leads to a larger NIH grant or philanthropic support for a more in-depth and long-term study of pediatric robotic therapy. 

Two Cook Children’s patients underwent gene-editing therapy for sickle cell disease (SCD) in 2024 through a clinical trial. The goal was to alter their DNA so that they start producing more fetal hemoglobin, which carries oxygen more efficiently than the misshapen red blood cells of a person with SCD.

One of the participants in that clinical trial, Ashlynn Malone of Little Elm, no longer experiences SCD pain since receiving a transplant of her edited stem cells at Cook Children’s Medical Center – Fort Worth in July 2024.

Before the transplant, Ashlynn often ended up in the hospital with a severe pain crisis. She had to be careful not to overexert herself, which tended to trigger the pain flare-ups. The severity of Ashlynn’s SCD made her a candidate for the RUBY Trial.

Thanks to that therapy last year at age 19, she’s now able to work, exercise and explore her passion for travel. Gene editing didn’t technically cure her disorder – but it has stopped the cycle of frequent pain episodes that was limiting her lifestyle.

“I can enjoy my 20s without having to worry about my health so much,” Ashlynn said. “I feel like my chains have finally been broken, and I get to do all the things I want to do.”  

An estimated 100,000 people in the United States have SCD, an inherited disorder in which red blood cells bend into a sickle shape, like the curve of a crescent moon. SCD causes pain, anemia, organ damage and other complications when those sickled cells tangle up in the blood vessels.

Cook Children’s hematologist Clarissa Johnson, M.D.  leads the Sickle Cell Program at Cook Children’s, which offers diagnosis, treatment, stroke screening, clinical trials and more.  

“It’s been encouraging in the last several years to see a lot more treatments that we can offer,” Dr. Johnson said. “Gene editing is a great example of how progress in science can improve the lives of patients. It’s also a great example of how the willingness to participate in clinical trials can help advance the field, because there had to be someone who said ‘I’m willing to try this’ when it was still very much an unknown.”

The RUBY Trial measured the safety and effectiveness of the experimental technology for editing genes of patients with SCD. Participants had their stem cells collected and sent to a lab on the East Coast, where the therapy manufacturer made tweaks to the cell composition. The next step was chemotherapy to make room for the body to receive the new cells. Then the participants received an infusion of their own cells edited to produce fetal hemoglobin – and healthier blood as a result. 

Departments across Cook Children’s played a role in the RUBY Trial, now concluded. The effort involved the research, apheresis, radiology, lab, pharmacy and hematology departments, along with the stem cell transplant physicians and team.

“Cook Children's involvement in the RUBY Trial has opened new horizons for gene editing therapy, offering hope and transformative possibilities for patients with sickle cell disease at our institution,” said Meg Moffer, coordinator of the Cellular Immunotherapy Program.

Dr. Johnson said gene-editing therapy is an exciting development that inspires hope for the future in SCD care. Every clinical trial involves risk along with the potential benefit, she pointed out.

“This has been a life-altering experience for the people who went through this clinical trial. I think they are pioneers to have the bravery to do that,” Dr. Johnson said. “As the clinician, I’m not the one who has to do the treatment. I can give the information, give the advice and encouragement, but they still have to be the person to say, ‘I’m going to give this a try.’

“To me that’s very brave, and I’m always very happy when someone takes that chance and the outcome for them is really good, which it has been for our patients.”

Ashlynn wanted to share her story as a tool to help educate the public about SCD. She urged patients to find out more about gene-editing treatment options.

“Do your research and look into it. It could be right for you. I’m happy that I went through with it,” she said. “I hope my experiences and journey through this treatment can help light up the way for other people who suffer from sickle cell.”  

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Megan and her brother Patrick battle Pompe disease, a rare neuromuscular disorder. Her father has spent nearly two decades raising money to fund research for drugs to fight Pompe. A story told in the movie, “Extraordinary Measures.”

The use of an experimental drug isn’t an uncommon practice at most major hospitals, including at Cook Children’s, including for Pompe disease.

For more than a decade, Cook Children’s has been involved with research for Pompe disease. Testing and treatment are available at the medical center. Treatment involves frequent intravenous infusions of enzyme replacement (Lumizyme). Enzyme replacement can slow the progression of the disease, as it has in many Cook Children’s patients.

Alglucosidase alfa was an approved drug indicated for use in patients with Pompe disease and marketed in the United States as Lumizyme and as Myozyme. Myozyme has been shown to improve ventilator-free survival in patients with infantile-onset Pompe disease as compared to an untreated historical control.

The drugs used for treatment for Pompe, like most of experimental medications under research at Cook Children’s, were pursued because our physicians wanted the capability to treat their patients in the best way possible. Most of the time, they weren’t opening a trial and then looking for patients to participate. They sought out the medication that would make a difference for their patients.

What is an experimental drug?

An experimental drug is a substance which may be useful to diagnose or treat disease or preserve or enhance health, but has not yet been approved by the U.S. Food and Drug Administration for the specific purpose of treating a patient.

“The drug might or might not be approved for one or a number of conditions, but it becomes ‘experimental’ when used to systematically investigate treatment for an unapproved condition,” said James Marshall, M.D., Chief Research Officer at Cook Children’s.

The importantance of 'informed consent'

The data obtained from the use of experimental drugs can be useful to future patients as doctors can see how beneficial they are the next time they are treating a patient with a similar condition.

At Cook Children’s, children participate voluntarily in all experimental drug investigations. Patients and their families, particularly in the case of minor children, must volunteer to participate in any experimental investigation through a process called informed consent.

Informed consent for children is regulated heavily by the U.S. and international governments. This type of consent is managed by a local board concerned only for the safety of research subjects, and far more comprehensive than the normal treatment consent process. Informed consent for children has several key elements:

• Education by the investigator and his/her team regarding all aspects of the research.
• Informed consent or actually signing a legal document by a minor child’s parent or legally authorized representative.
• Assent or documenting that a minor child understands and agrees to participation, and a continuous, open and welcome ongoing conversation between the participant/family and the investigational team to assure understanding through all phases of the research.

The initial consent/assent process can take several hours, and investigators never really consider the conversation to be closed. Patients and their families often learn more about their condition during the consent/assent process than they would by receiving treatment only. Patients and families can decide to stop participation even before the experimental drug is administered.

However, many patient families see the importance of participating in these experimental drugs and the benefit it may bring to not only their child, but to patients in the future.

“At Cook Children’s, we believe that all children deserve the best, evidence-based treatment strategies available to manage their illnesses and maintain good health,” Dr. Marshall said. “Cook Children’s patients have the opportunity to contribute to the health of other children through safe and ethical clinical research. We treasure the fact that clinical research is the essence of people voluntarily caring for the future of mankind.”

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More about Clinical Research at Cook Children's

At Cook Children's, we believe that all children deserve the best treatment strategies available to manage their illness and maintain good health. Our research environment applies leading-edge scientific knowledge, technology and evidence-based practice to improve quality care outcomes for children. Click here to learn more.