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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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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Her whole life, 19-year-old Ashlynn Malone has struggled with fatigue, outbreaks of severe pain, and hospitalizations due to sickle cell disease (SCD). 

That’s why Ashlynn jumped at the chance to join a clinical trial designed to stop her SCD symptoms by modifying her blood stem cell genes. Ashlynn has early access to the treatment at Cook Children’s Medical Center – Fort Worth, the RUBY Trial’s only pediatric site in Texas.  

The RUBY Trial uses an experimental technology called EDIT-301 for editing genes. Cook Children’s hematologist Clarissa Johnson, M.D. said preliminary results show the EDIT-301 treatment provides long-lasting relief from the painful flare-ups and anemia that patients like Ashlynn experience when their blood flow is blocked by sickle-shaped red blood cells. 

“This is a more potent treatment than what we have been able to offer thus far,” said Dr. Johnson, who heads up the Sickle Cell Program at Cook Children’s, which serves about 400 patients. “It’s not a cure, but a transformative treatment.”

The first RUBY Trial transplant at Cook Children’s was done in January 2024. Ashlynn will be the second. Cook Children’s is now working to enroll qualified patients ages 12-17 because the enrollment for adults has closed.

“The trial was always planned to include adolescents,” Dr. Johnson said. “We were chosen because I pursued this for our patients, and we were able to demonstrate to the company that we had the expertise and resources to conduct this trial with great support from our research department.”

How does EDIT-301 work? Through technology that edits the genes involved in SCD to make them able to produce healthier blood cells. The RUBY Trial is a study that measures the safety and effectiveness of that treatment.

Gretchen Eames, M.D., serves as Medical Director of the Stem Cell Transplant Program at Cook Children’s. Dr. Eames said the program has an extensive track record since 1985 of providing leading-edge therapies and caring for patients with SCD. 

“Our outcomes as well as our superb and experienced research team are the reasons we have been chosen to participate in clinical trials such as the RUBY Trial,” she said. “We jumped at the chance to bring this transformative therapy to the patients of North Texas and beyond.”

Previously, the only definitive therapy for SCD was undergoing a stem cell transplant from a family member -- a much more intensive therapy, with greater risks. EDIT-301 eliminates the need for a matched donor since it uses the patient’s own cells.

“Now we have a gene therapy that can give hope to those patients who do not have a family bone marrow donor or who are ineligible to receive a traditional bone marrow transplant,” Dr. Eames said.

Ashlynn met the criteria to enroll in the RUBY Trial in 2023. Her stem cells were collected at Cook Children’s and shipped to the manufacturer’s lab. After about 12 weeks, the edited genes will be shipped back to Fort Worth and infused into Ashlynn’s blood. Then she’ll go through follow-up testing for at least two years.

She has confidence in her doctors -- and she’s hopeful that the treatment will end her SCD pain and exhaustion. Ashlynn knows she’ll need some chemotherapy before the infusion, and there are potential side effects, but she says the risks are worth the expected outcome.

“I can’t wait to be done with sickle cell,” she said. “I’m more excited than anything.”

Here’s a closer look at the potential for this treatment to expand the genetic therapy options for people living with severe SCD.

Three Treatment Phases

An estimated 100,000 people in the U.S. have sickle cell disease, an inherited disorder most common in people of African descent. A mutation in the patient’s genes causes the hemoglobin proteins – the body’s oxygen transporters -- to bend so that the red blood cells curve like crescent moons instead of round discs. Instead of flowing smoothly through the blood vessels, the sickle-shaped cells get clumped up. It causes pain and can lead to anemia, organ damage or stroke.  

Dr. Johnson said the EDIT-301 treatment targets the genes that makes fetal hemoglobin. Adults with healthy hemoglobin don’t usually need fetal hemoglobin. The treatment tweaks the genes so that they start producing very high levels of fetal hemoglobin to counteract effects of the sickled hemoglobin.  

The clinical trial spans about 2½ years and consists of three parts:

1. Phase One: Selected candidates are injected with a medication that moves their blood stem cells out of the bone marrow. An intravenous line collects the stem cells, which are sent to the Editas Medicine laboratory, where genes from those cells are edited via CRISPR technology.
2. Phase Two: After the cells are edited and shipped back to the trial site, the patient receives four days of chemotherapy to wipe out any remaining stem cells in their bone marrow. “Think of it like a garden,” Dr. Johnson said. “You have to clear out the garden to make room to plant something new.” Cells with the edited genes are transplanted into the body and travel to the bone marrow. The patient remains hospitalized until they can consistently create white blood cells to reduce risk of infection and are not needing frequent transfusions of red blood cells and platelets.
3. Phase Three: Follow-up tests check for any side effects and measure the impact of the treatment on the patient’s blood quality, heart and lungs.  

Results are encouraging from other sites nationally where the clinical trial started earlier, according to Dr. Johnson and Dr. Eames. The edited cells have increased the production of fetal hemoglobin in most participants in the study, leading to fewer SCD complication and improved quality of life.

Departments across Cook Children’s play a role in the RUBY Trial. The effort includes the research, apheresis, radiology, lab, pharmacy and hematology departments, along with the stem cell transplant physician and team. 

Ashlynn’s Perspective

Ashlynn was born with SCD because both of her parents carried the genetic trait. One cousin also has the disorder, but no one else in her family.  She’s a patient of hematology/oncology physician Timothy McCavit, M.D., who directs the Bleeding Disorder Program and Hemophilia Treatment Center at Cook Children's.

“I was never really able to do things other children were able to do because I had physical limitations,” she said. “When I was younger, I was prone to getting sinus infections because my immune system wasn’t as strong. If I push myself too hard, that could cause me to have a pain episode. So I always had to limit myself.” 

Hard exercise, stress or allergies can bring on an SCD pain episode for Ashlynn. She described the sensation as an aching in her back, head, arm … anywhere in her body. Sometimes the pain is sharp.

To control mild pain, she takes Tylenol. She’ll take a prescribed medication for moderate pain. And if that doesn’t work within a day or two, she goes to the Emergency Department. She estimates she’s been 50-100 times to different hospitals, including Cook Children’s Medical Center – Prosper, a short drive from her home in Little Elm.

“I have a natural high pain tolerance. If it gets to a point where I feel like I’m going to start crying, that’s when I know it’s getting bad,” Ashlynn said.

She first heard about the RUBY Trial during one of her hospitalizations last year, when Dr. Johnson brought it to her and her mom’s attention. Ashlynn was eligible because the medications she was taking for SCD didn’t stop her frequent pain episodes.

Optimistic that the clinical trial would help, she was screened and accepted. Her stem cells were collected in January 2024, placed in an ice chest, and shipped to the Editas Medicine lab.   

She has received regular transfusions of donated blood while waiting for her edited genes to be shipped back, likely by April. Ashlynn looks forward feeling well enough to reach her goals: Travel to Japan, start working out, and own a business. She’d like to spread awareness of SCD.

“If you know someone who has sickle cell disease, just know there are going to be some days when they’re not really going to want to hang out or do much physical activity,” she said. “Just be more understanding about it.”

Bringing Hope

SCD can complicate school, work, travel and other plans because a pain episode can happen at any time. That’s why a treatment like EDIT-301 gives hope to patients and families dealing with the interruptions and stress that chronic illnesses cause.

“Having a chronic illness is very consuming, not just for the child who's affected, but also for the family,” Dr. Johnson said.

Many parents tell her they’re excited about genetic therapy because of the prospect of making long-term plans without worrying about their child’s SCD flaring up on a trip, for instance. Some families, however, are more hesitant. 

“It's a big decision,” she said. “We know that not everybody's going to necessarily be first in line. But I think the longer we see this out there and see the difference it makes for people, that will be what encourages others to give it a try.”

After the RUBY Trial ends, the manufacturer may choose to submit the data to the U.S. Food and Drug Administration for approval of the treatment. 

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Grey Gutierrez has a rare genetic disorder that makes his muscles weak, but he doesn’t let Duchenne muscular dystrophy (DMD) keep him off the playground.

The spunky San Antonio 9-year-old uses a wheelchair at school to get from classroom to classroom so that he can save his strength for recess. It’s a strategy – along with physical therapy and medication – that helps Grey keep up with his friends.  

Grey’s battle against DMD includes another tool: Research. In 2019 he enrolled in a clinical trial at Cook Children’s for a medication under development. That trial failed to achieve its goals and the medication was not brought to market.  Grey recently joined a second research study at Cook Children’s.

Worldwide about 20,000 children like Grey are diagnosed with DMD each year. Their bodies don’t produce a protein called dystrophin, which is needed to form and maintain healthy muscles. The disease causes children as young as age 2 to begin having trouble walking or running.  Eventually their heart muscles and breathing break down. But treatments can slow the symptoms.  

Grey’s mom, Marina Teissere, says their family chooses to participate in research despite the possibility of harmful side effects.

“To get medicine to the market takes years. Grey doesn’t have that much time to wait,” she said. “Our best bet is through these clinical trials to get him the medicine before it’s available elsewhere. This is the only way I believe that these kids can get access to it. Otherwise, it’ll be too late.”

Five neuromuscular studies are currently underway at Cook Children’s under the leadership of Stephanie Acord, M.D. and Warren Marks, M.D. Dr. Acord is director of Neurorehabilitation and medical director for the Neuromuscular Medicine and Muscular Dystrophy Association clinics at the Jane and John Justin Neurosciences Center. Dr. Marks is medical director for Movement Disorders.

“It’s patients like Grey and his family that help medicine and treatments continue to advance,” Dr. Acord said. “Without their participation and support, treatment options become stagnant.”

 Seventy-three patients, including Grey, participated in 2023 in the neuromuscular trials at Cook Children’s.  Additional clinical studies are planned for 2024.

Clinical trials nationwide have led to advances that prolong life expectancy and improve quality of life for people with neuromuscular disorders, Dr. Marks said. When patients meet a study’s selection criteria – including genetics, age and other factors – Cook Children’s wants to give them the option to sign up.

“We are trying very hard to offer the latest therapies that are approved as well as promising new therapies that haven’t been released yet, fully understanding that some of them will never come to fruition,” he said. “We think it’s important to at least offer choices to families.”  

Grey comes to Cook Children’s in Fort Worth twice a year to see the neuromuscular experts, as well as respiratory, cardiology and endocrinology specialists. He’s a big fan of Camp MDA, where he went fishing and made pottery last summer alongside other kids with muscle disorders. DMD tires out his body but not his imagination and curiosity. Here’s his journey.  

Determining the Diagnosis

As a baby, Grey was a little slow to roll over and crawl. He hit other developmental milestones such as talking on time. His parents weren’t worried until the teachers at day care noticed Grey had trouble climbing the playground equipment. He tended to drag his right foot. He tripped and fell easily. 

X-rays didn’t show any skeletal problems. Grey was still a toddler; Marina figured that whatever was going on, he would outgrow it.

But at age 4 came a new concern about bowel movements and constipation. His pediatrician in San Antonio ran blood tests. Grey’s level of a liver enzyme, creatine kinase (CK), was extremely high. Injured muscle cells release CK into the blood, and Grey’s elevated level pointed to DMD.

That suspicion led Grey’s family to neurologists in Houston, where the diagnosis was confirmed. He started physical therapy. Meanwhile, Marina searched online and came across a clinical trial Dr. Marks was heading up at Cook Children’s. Grey joined that 2019 study, which explored a medicine designed to reduce or eliminate the need for steroids in DMD cases.

“He had to take three pills three times a day. We needed to make sure he took the medicine right on time and had a lot of high-fat snacks,” she said. “Grey was a trooper.”

Treatment and Another Trial

After that study ended, Grey kept coming to Fort Worth for follow-up appointments because his parents appreciated how the neurology team cared for him during the yearlong clinical trial. What else impressed Marina? That doctors at Cook Children’s are advocates for research.

For ongoing treatment Dr. Marks put Grey on deflazacort, a corticosteroid that reduced the drastic mood swings caused by a previous prescription. Marina thinks deflazacort has slowed down his progressive muscle weakness.

 “The research says it adds maybe three to five years of additional mobility. We’ll take it,” she said. “It means he gets to be that much more mobile for that much longer.”

These days Grey does physical therapy in the gym and swimming pool, along with occupational therapy and recreational therapy through a rehabilitation center in San Antonio. He’s a third-grader with a passion for science, art and animals. Ask him about Camp MDA, and he’ll tell you “it was really fun.” His heart remains strong, and he doesn’t use breathing devices, although it’s tough to cough when he gets sick.

In 2023 Grey started a second clinical study at Cook Children’s. This one analyzes a new medication that aims to preserve and regenerate muscle strength. His parents talked to him about the possible pros and cons. Grey was in favor because he wants more ability to run and less time in the wheelchair.

“It’s taking a risk. But I just think we take that risk, or we do nothing and then it’s too late,” Marina said. “We make sure he knows what’s happening. We make sure that he’s aware of what he’s taking and what it could potentially do or potentially not do, and he seems to be OK.”

More about DMD

Cook Children’s sees about 75 boys with DMD, some from out of state. If a child is toe walking, the family might have consulted an orthopedist first before being referred to neurology for DMD testing. Early diagnosis is helpful, Dr. Marks said.

He applauds the work done by the neuromuscular team at Cook Children’s, which consists of Dr. Acord and Dr. Marks along with Brittney Rhem, M.D.; Marcie Baldwin, RN CPNP; coordinator Megan Batts, RN; Angela Pomykal, PT; and Lindsay Luker, PT at the Motion Analysis Lab.

A new approach to treating DMD became available in June 2023 when the U.S. Food and Drug Administration approved a gene therapy called Elevidys for patients ages 4-5 years old. CRISPR technologies to modify DNA are also being explored. Dr. Marks wants parents to know that treatments will continue to improve as research unlocks the mysteries of neuromuscular disorders.

“When I first started with MDA several decades ago, the messaging was 'The cure’s around the corner.’ The mantra became ‘We just need to keep you stronger until the next thing comes along,’” Dr. Marks said. “Now the cure is closer.”