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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Miller Queen suffers from a severe and debilitating form of epilepsy known as Dravet syndrome, but you’d never know it by looking at him. At 7 years old, Miller is doing things that never seemed possible like playing soccer and going to school.

“Daily life when you don’t have seizure control is just a rollercoaster,” his mother Chelsea Queen told NBC 5. “You’re kind of always on edge waiting on the next seizure to happen.”

Starting at 6 months old, Miller was having as many as 10 seizures a day. Every treatment he tried failed and his parents were afraid to take their eyes off of him for even a moment.

Then, they found Cook Children’s and M. Scott Perry, M.D.,  an epileptologist and medical director of Neurology and the Genetic Epilepsy Clinic at Cook Children's.

“When you deal with epilepsies that are so difficult to control, it certainly becomes difficult not to feel that there’s not an answer,” Dr. Perry said.

Miller was enrolled in a clinical trial for the drug fenfluramine, which was once used as a popular appetite suppressant. Only a handful of hospitals nationwide were involved in the trial and Cook Children’s happened to be the only one in Texas. The drug completely stopped Miller’s seizures.

“The treatment completely changed his life,” Queen said in the interview with NBC 5. “He’s always been such a happy kid but now he’s able to experience life to the fullest.”

Overall, the clinical trial showed fenfluramine reduced seizures on average by about 70%. The research helped lead to approval from the Federal Drug Administration, opening up fenfluramine as a treatment for everyone with Dravet syndrome.

“The next medication to try and make you seizure-free is probably 2%, but you know what, you might be that 2% so that’s why we keep looking for it,” Perry said.

For Miller’s parents, they know this to be true.

Matt Queen, Miller’s father told NBC 5 “If something doesn’t work, don’t lose hope.”

A rare disease is defined as any disease affecting fewer than 200,000 people in the U.S.¹ While individually, each of these diseases is rare, as a group, they are quite common. As many as 1 in 10 individuals may have a rare disease and half of those are children.

Importantly, up to 80 percent of rare diseases have a genetic basis yet only 5 percent of these diseases have treatments.² For these reasons, it’s important to bring awareness to rare diseases and to continue developing expertise and support for research to find cures.

M. Scott Perry, M.D., medical director of Neurology and the Genetic Epilepsy Clinic at Cook Children’s, discusses some of the rare diseases he cares for and how bringing awareness to these conditions can impact patients with other conditions.

What are some of the rare diseases you encounter in your Genetic Epilepsy Clinic?

Two of the most common conditions I treat are Tuberous Sclerosis Complex (1 in 6,000) and Dravet Syndrome (1 in 20,000), though I encounter a variety of other rare genetic-based epilepsies on a daily basis. Tuberous sclerosis is estimated to affect approximately 50,000 people in the U.S and presents with a variety of tumors that can grow in the heart, brain, kidneys and eyes – as well as skin manifestations, seizures, and delays in development. Dravet syndrome may affect as many as 1 in 16,000 children in the U.S. and presents with seizures – often prolonged seizures with fever initially which evolve to multiple other seizure types including tonic - clonic, absence, myoclonic and “drop attacks” by age 2 years. Children are often normally developing initially but demonstrate a slowing or decline in development after onset of their seizures. For both of these conditions, the epilepsy is a major component and often seizures are resistant to the available treatments – thus one reason for continued research.

How have you seen research into these conditions change treatment?

So often with neurological conditions, especially epilepsy, we’ve focused on treating the symptoms – meaning the seizures. Both of these conditions have a genetic basis that results in seizures, but also a host of other problems such as difficulties walking, problems with sleep cycles, behavior, and feeding for example. By understanding the genetic basis of the disease, we hope to develop therapies targeted at the source of the condition, such that multiple symptoms can be treated and one day the disease cured. For tuberous sclerosis, understanding the genetic mechanism of the disease led to the development of everolimus, a drug that targets an important step in tumor development in this condition. By using this drug, we now have a way to stop or slow the growth of some of the tumors in this condition. The drug has also shown ability to reduce seizures in children with tuberous sclerosis.

For Dravet syndrome, several new drugs have been investigated and either approved (Epidiolex®/cannabidiol) or submitted for approval (Fintepla®/fenfluramine). These drugs, along with stiripentol (approved 2018), are the first drugs to be studied and approved specifically for Dravet syndrome. We know the gene which causes the majority of Dravet syndrome is SCN1A which encodes a sodium channel important to brain function. Researchers are now developing treatments which target genes which regulate how much SCN1A is made to increase the availability of healthy SCN1A in these patients. This treatment (antisense oligonucleotides) gets at the root cause of the condition and holds potential to treat seizures and many other complications of the disease – potentially reversing it completely one day.

Does Cook Children’s participate in research for rare conditions?

Absolutely. In Neurosciences we have recently participated in trials of both Epidiolex and Fintepla for Dravet syndrome and Lennox Gastaut syndrome. We are preparing to launch additional drug trials this year for these conditions as well. I have been working with researchers to develop trials for antisense oligonucleotides mentioned earlier. We are also planning to start a trial for CDKL5, another rare form of genetic epilepsy and we participate in collaborative studies of tuberous sclerosis.

Why is it important to study rare diseases?

As we said earlier, while these diseases are rare they are actually quite common as a group. As many of these diseases have a genetic basis, research into cures directed at this genetic etiology potentially hold clues to curing a number of conditions. If we can find a method to correct the gene dysfunction in Dravet syndrome, then we may be able to apply the same science to cure other genetic epilepsies such as SCN2A, SCN8A, KCNQ2-related epilepsy, etc.

What are you most excited for in the coming year for treatment of rare disease at Cook?

This summer we plan to open our Adult Genetic Epilepsy clinic. One of the great things about research into rare diseases is that we are now seeing kids with these rare syndromes live to be adults. The downside is that adult providers have never had experience with many of these conditions and are mostly unprepared to care for them the way we do. In addition, we don’t know a lot about how these rare epilepsies act in adulthood – do they develop new or unique symptoms as adults that we didn’t see as children? The Adult Genetic Epilepsy clinic will be staffed by myself and an adult epileptologist who will work with me to care for these patients – ultimately developing the expertise needed to provide the best care as they transition to adulthood. We hope to use this clinic as a model for other institutions to implement similar clinics in the future.

1. FDA Office of Orphan Products Development.
2. “Rare Diseases and Orphan Products: Accelerating Research and Development” Committee on Accelerating Rare Diseases Research and Orphan Product Development Board on Health Sciences Policy.

Cook Children’s recently participated in multicenter studies of the drug in treatment of patients with Dravet syndrome and is currently enrolling patients in a study for Lennox Gastaut Syndrome.

The research trials sponsored by Zogenix focus on a low-dose, liquid solution of fenfluramine, which was previously used in “fen-phen” for obesity and ultimately taken off the market following evidence it was related to adverse effects on heart valves.

Dravet syndrome affects an estimated 20,000 patients in the United States. Dravet results in a severe epilepsy with seizures typically resistant to treatment with currently available therapies.

The trial found that fenfluramine reduced the frequency of convulsive seizures by a median 62.7 percent, compared with a 1.2 percent median reduction in patients taking placebo, meeting the main goal of the trial.

Dr. M. Scott Perry, medical director of Neurology and Director of the Genetic Epilepsy Clinic at Cook Children’s said, “This drug is a game-changer for patients suffering from Dravet Syndrome. Rarely do we get a treatment for epilepsy which reduces seizures so significantly, especially in an epilepsy syndrome that is this refractory to therapy. I can’t wait to see if the results are as remarkable for Lennox Gastaut Syndrome.”

Thus far, no significant cardiac valvulopathy or pulmonary hypertension has been noted in trials for epilepsy, possibly due to the lower dosing used in these trials.

Zogenix will now focus on submitting applications for a marketing approval of its drug in the U.S. and Europe in the fourth quarter of 2018.

A panel convened by the FDA voted 13-0 that the agency should approve the drug as treatment of these two rare forms of epilepsy. The FDA will make a final decision to approve the medicine by June 27.

Cook Children’s participated in several of GW Pharmaceutical’s clinical trials of Epidiolex used to treat children over the age of 2 with Lennox Gastaut and Dravet and continues to enroll children in a trial of the drug for treatment of seizures in Tuberous Sclerosis Syndrome. “The trials were the largest of their kind in the world and have provided the gold-standard evidence needed to prove cannabidiol can be effective as a treatment for epilepsy,” said M. Scott Perry MD, Medical Director of Neurology and principle investigator for the trials performed at Cook Children’s.

The FDA gave the drug a favorable review, stating that it provides “substantial evidence” of the drug’s effectiveness in treating Lennox-Gastaut syndrome and Dravet syndrome.

“Although the review is still ongoing, the risk-benefit profile established by the data in the application appears to support approval of cannabidiol for the treatment of seizures associated with LGS [Lennox-Gastaut syndrome] and DS [Dravet syndrome]," the FDA said in a report.

Dr. Perry explains that Epidiolex is an essentially pure CBD substance produced under strict standards to ensure the drug is the same with every batch. Once approved, the drug would be obtained from a pharmacy, prescribed by a doctor and more likely to be covered by insurance.

“My hope is this will be the first of many drugs derived from the cannabis plant,” Dr. Perry said. “This drug has gone through a rigorous process to be approved and I think it will help people feel safe taking the medication. I hope it also encourages more research into what the hundreds of other substances in the cannabis plant can do for patients.”

Previously On This Topic:

• 9 Facts about Cannabidiol (CBD) Oil and the Texas Compassionate Use Act
• Texas legalizes non-euphoric cannabdiol for seizures in epileptic patients
• Drug in Cook Children's epilepsy trial shows positive results in separate trial
• Success in CBD study: Cook Children's researchers play a vital role
• Cannabis oil trial ongoing at Cook Children's
• Study: Cannabis Oil Can Dramatically Decrease Epileptic Seizures

What are some of the presentations of SCN2A-related disorders? Children with SCN2A can often present with epilepsy which may manifest in several levels of severity. SCN2A was first discovered as a cause of benign familial neonatal infantile seizures (BFNIS), a syndrome presenting in multiple family members with seizure onset as neonates and infants with normal developmental outcome and good seizure control. Later, SCN2A was discovered as a cause of infantile spasms and other early onset severe epilepsies of childhood, the so-called early infantile epileptic encephalopathies. SCN2A has been implicated as one of the causes of Ohtahara Syndrome, Dravet Syndrome, Migrating Partial Epilepsy of Infancy and West Syndrome amongst others. Finally, SCN2A has been found to be a major cause of intellectual disability, schizophrenia, and autism which may occur in the absence of epilepsy.

What is the cause of SCN2A-related disorders? SCN2A is a gene which encodes a sodium channel found within the initial segments of neurons. This location is important to determining whether a neuron will generate a signal or not, thus a reason mutations can present with neurological symptoms. Most mutations in SCN2A are de novo, meaning they occur spontaneously and were not inherited from the parents. This is often the case in more severe disease presentations. SCN2A may be inherited in an autosomal dominant manner in more benign presentations such as BFNIS.

How are SCN2A mutations diagnosed? Diagnosis is made using genetic testing in patients with appropriate clinical features. MRI is often normal and EEG findings may vary.

Is there a treatment for SCN2A-related disorders? Unfortunately, there is not yet a cure for SCN2A-related disorders. Certain sodium channel drugs (for example, phenytoin, lamotrigine) have demonstrated more favorable responses for seizure control in some patients, while in others sodium channel drugs may aggravate seizures. This may be due to how the mutation impacts the function of the sodium channel (gain of function versus loss of function). Aggressive control of seizures with a clear rescue plan for prolonged seizures is important. Other manifestations such as movement disorders, dysautonomia, and neurobehavioral manifestations can be managed to some degree with medications and therapy.

What other problems might be found in patients with SCN2A disorders? In addition to epilepsy and developmental delays, other manifestations of SCN2A can include movement disorders such as dystonia, abnormal gait, ADHD, autism, dysautonomia (i.e. problems with heart rate, blood pressure, and temperature regulation), and GI problems such as feeding difficulties or reflux.

For more information about SCN2A and SCN2A Awareness Day, visit www.scn2a.org.

The bill required DPS to license at least three dispensing organizations by Sept. 1, 2017, should they meet requirements.

On Feb. 8, 2018, the first medical dispensary in the state of Texas will open.

What does all of this mean for children with epilepsy?

1. What is it in the cannabis plant that helps treat epilepsy?

The truth is we don’t yet really know. There are over 500 chemical compounds in the cannabis plant and over 100 of them are plant-based cannabinoids (phytocannabinoids) which may interact with the endocannabinoid system of the human body and treat disease. Cannabidiol (CBD) is a non-psychoactive component (i.e. does not produce a “high” feeling) and has been most widely studied so far for epilepsy. It does not interact with either of the two known cannabinoid receptors in the brain and its mechanism is still unclear. Tetrahydrocannabidiol (THC) is the component in the plant that produces a high and does interact with the cannabinoid receptors, but for many reasons, is not likely to be a good choice as an antiepileptic compound.

2. What is CBD oil and what types of CBD oil are now legal in Texas?

A CBD oil is an oil made from a cannabis plant that is high in CBD and typically lower in THC. The oil may contain amounts of multiple other compounds found in the plant as well. The 2015 Texas Compassionate Use Act allows for “high” CBD (more than 10 percent by weight)/”low” THC ( less than 0.5 percent by weight). This is slightly higher than the amount of THC (less than 0.3 percent) allowed in a plant to be considered hemp. Hemp oils are produced from these lower THC plants and are often a poor source of CBD but have been legal and widely available.

3. People on the Internet already say CBD oil works, so why aren’t all doctors OK with using it over typical medications prescribed for seizures?

All FDA approved antiepileptic medications have gone through rigorous studies to prove they work and they are safe to use. The studies are blinded and placebo-controlled which means neither the doctor nor the patient knows whether they are getting the real drug or a placebo until the study is complete. This helps remove bias (i.e. people feeling like their seizures are better because they know they are taking the real drug). It also helps separate which side effects are due to the drug and which occur randomly in the course of life (for example fevers, rash, nausea which can occur commonly regardless). CBD has only recently been tested in this type of rigorous study – more on this later – and the other components of the plant lack this type of research so far.

4. If CBD has already been studied, why are some doctors still hesitant to recommend CBD oil?

When people are treated with typical antiepileptic drugs, they are taking a single compound, like carbamazepine or levetiracetam for example. When you get a CBD oil, you get a substance that may have a high amount of CBD, but it also can contain varied amounts of the multiple other compounds from the plant. We do not know how effective and safe those other compounds are, so we must be cautious to recommend it to treat your child. Currently, there are no testing standards to make sure the CBD oil you get from a company contains what the label says, thus the formulation may change some from month to month – something akin to getting a different generic antiepileptic medication each month. While all CBD oils contain the similar CBD compound, they may be produced from different types of plant, using different growing techniques/conditions, and manufactured with different processes – thus creating different medications with different other compounds included. Think of it as being prescribed a sodium-channel drug like carbamazepine, but potentially getting one of multiple other sodium channel drugs such as oxcarbazepine, phenytoin, rufinamide, lamotrigine, etc. So doctors aren’t necessarily averse to CBD oils, we just have to be realistic about their limitations.

5.What did the studies of CBD show?

First, understand that the Greenwich Biosciences CBD compound Epidiolex is not the same as the CBD oil you get from a dispensary. It is a nearly pure CBD substance produced under strict standards to ensure the drug is the same with every batch. In 120 patients with Dravet syndrome, 43 percent on CBD had more than 50 percent reduction of convulsive seizures versus 27 percent on placebo. This was actually not a statistically significant difference. In 171 patients with Lennox-Gastaut syndrome, 44 percent on CBD had more than 50 percent reduction of drop seizures versus 23.5 percent on placebo and this was significant. From these results we can conclude that CBD does appear to have some antiseizure effect, but it is not necessarily any better than most other available drugs. It is also not without side effect, as diarrhea (19%), sleepiness (15%), fever (13%), decreased appetite (13%), and vomiting (11%) were reported. So CBD is an option for epilepsy treatment, but is not likely to cure every patient.

6. How does the Texas Compassionate Use Act work?

Under this law, doctors can register to recommend CBD oils only to patients with intractable epilepsy. To register, a doctor must be board certified in Neurology or Child Neurology and must also be certified in Epilepsy/Neurophysiology or spend more than 50 percent of their practice treating patients with epilepsy. If a registered doctor feels CBD oil is appropriate for their patient because the patient has tried all reasonable, better-studied and available treatment alternatives, the doctor can recommend an amount of CBD to be taken. This recommendation must be approved by a second registered doctor who reviews the case and agrees with the decision. Registered patients can then go to one of three dispensaries in the state to get a CBD oil.

7 .Will the CBD oil be covered by insurance?

No. As this is not an FDA approved treatment, it is unlikely any insurance company will cover the cost. The price is typically several hundred dollars per month depending on the amount of CBD recommended.

8. Now that we have this law, it is legal right?

The cannabis plant and all the components of the plant remain a schedule 1 substance on the Drug Enforcement Agency’s list- meaning it has no medicinal value and is illegal. CBD is part of the plant and still falls under this category for federal law despite what a state law may say. While the 2013 directive from the Department of Justice indicated they had better things to do than prosecute people following the laws of their state, Jeff Sessions reversed this opinion several weeks ago – thus it is unclear how the federal government will choose to deal with CBD oils now.

9. When will a pharmaceutical grade CBD oil be available?

Greenwich Biosciences has submitted their drug, Epidiolex, to the FDA for approval December 2017. While the FDA could take years to rule, they have indicated their plan is to rule on approval by summer 2018. Once approved, this drug would be obtained from a pharmacy, prescribed by a doctor, and more likely to be covered by insurance.

Previously on this topic:

• Texas legalizes non-euphoric cannabdiol for seizures in epileptic patients
• Drug in Cook Children's epilepsy trial shows positive results in separate trial
• Success in CBD study: Cook Children's researchers play a vital role
• Cannabis oil trial ongoing at Cook Children's
• Study: Cannabis Oil Can Dramatically Decrease Epileptic Seizures

Fenfluramine was originally used as a weight-loss drug before being pulled from the market in 1997 with reports that it caused severe damage to the heart.

Now being used at lower dosages, clinical trials in the United States, Canada and Europe have found the drug to be highly effective in the treatment of seizures in Dravet syndrome.

The results from the randomized, double-blind, placebo controlled phase 3 trial of Zogenix ZX008 (previously known as fenfluramine) showed it to be effective in the treatment of seizures in Dravet syndrome. Dravet syndrome is a rare, devastating epilepsy syndrome of childhood presenting with multiple seizures types, often resistant to most antiepileptic drugs (AEDs).

The most recent study included 119 patients between the ages of 2-18 years. After a six-week baseline, patients were randomized to placebo, a lower dose (0.2 mg/kg/d) or a slightly higher dose (0.8mg/kg/d) group added to their existing AEDs, which remained stable throughout the study.

Seventy percent of patients had a greater than 50-percent reduction in convulsive seizures in the high dose, 41 percent in the low and only 7.5 percent in placebo. Forty-five percent of the patients who participated had more than a 75-percent reduction in the high dose, 20.5 percent in the low, and 2.5 percent in the placebo. Finally, the high dose group experienced 20.5 days of seizure freedom as the longest median duration, 14 days in the low dose and only 9 in placebo.

This is intriguing news locally because Scott Perry, M.D., an epileptologist and medical director of the John and Jane Justin Neurosciences Center at Cook Children’s, is leading a second similar study at Cook Children's.

Currently, six patients are participating in the study at Cook Children's and the study remains open for enrollment. The study is open to children with Dravet syndrome with seizures uncontrolled on current AEDs.

"A number of inclusion/exclusion criteria are required to be selected for the trial. Patients may not be using cannabidiol (CBD) and they can’t have preexisting cardiac abnormalities because of past cardiac valve problems with the drug used as a diet pill," Dr. Perry said. "Based on the early open label results published from Belgium which prompted this present study, I’m quite excited. I’m pleasantly surprised that the results of this blinded/controlled trial were very favorable, much like the early open label results suggested. These children have a catastrophic form of epilepsy for which seizure control is very unlikely. This drug has demonstrated significant reduction in seizures which would be considered successful in any epilepsy syndrome. The results are that much more impressive given the difficulty these patients have in gaining seizure control.”

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What Is Dravet Syndrome?

Dravet Syndrome is a rare genetic epilepsy (1 in 25000) that begins in the first year of life with seizures in the setting of fever. Unlike typical febrile seizures, children with Dravet syndrome often seize every single time they have fevers.

They may also seize when they have mild elevations of temperature, for instance, after taking a hot bath or after being outside on a hot day. They are normal developing and healthy in that first year of life, despite the fact they have frequent febrile seizures. These seizures can be very long lasting, 30 minutes or longer.

Their initial seizures are often characterized as hemiclonic seizures, so they’ll be seizing on the right side of the body at one time and the next time they come in, it’s predominately on the left side. After the age of 1, they begin to have seizures in the absence of fever. They have multiple seizure types at that point including absence, generalized tonic clonic seizures, atonic seizures and tonic seizures. The seizure frequency often increases, their EEGs become progressively abnormal and the children themselves can have a stagnation in their development or even a decline in development as the epilepsy progresses.

In the first 10 years of life or so, seizures can be quite frequent and very difficult to control. Generally after that time the seizures slow down, but will still occur throughout life.

What are the current treatment options of Dravet?

The mainstays of treatment of Dravet syndrome are medications. The first being valproic acid (Depakote), another clobazam (Onfi), and another one called stiripentol. Beyond those three primary medicines, there are other medications that can be used with variable success in addition to dietary therapy and recently, medical cannabis or cannabidiol, has shown some promise.

Importantly, there are medications that are used to treat epilepsy that should not be used to treat children with Dravet syndrome. Those are medications that work on the sodium channels. Because the syndrome is a disorder of sodium channels, using medications that work on sodium channels actually makes these kids much much worse. Carbamazepine, Oxcarbazepine, and Lamotrigine are a few of the medicines that work on sodium channels that should be avoided in children with Dravet syndrome.

Does that happen often? That people put these kids on those medications?

Unfortunately, yes. Because those medications are typically used for focal onset seizures and when these kids first present they are having focal seizures people treating them logically say, "Well let’s put them on oxcarbazepine." When these kids get worse the next logical reaction to that is that they say, “Oh they are worse. Let’s give them some more. They must not have enough.” Then they get even worse. That’s actually one way that some of these kids get diagnosed. People recognize that these sodium channel drugs made them much worse, so maybe they have a sodium channel disorder.

I have been guilty of making this mistake. So even in my immense knowledge of this disorder, I have made this mistake.

What impact does Dravet have on the entire family?

It’s interesting that you bring that up because we actually did a project with the University of Washington in Seattle about caregiver burden of caring for Dravet Syndrome. We developed a scale that they are in the process of standardizing for clinical use. These families have difficulties caring for their other children because they can’t spend as much time on the activities of the other kids because they spend so much time focusing on the health care and safety of their kid with Dravet syndrome. Jobs, it’s difficult for both families members to hold down a job because somebody usually has to stay with the child. I imagine it’s difficult for the parents themselves to get much time with each other because one is probably up most of the night worrying about their child, while the other one is up most of the day. The amount of time lost from work and other obligations, community obligations, etc. caring for the child is pretty significant.

And it impacts the siblings too, right?

Exactly. They may not get to do all the things that they want to do. Or if they do get to do those things, if they do want to play baseball, maybe the family can’t take them to baseball all the time. So it’s your neighbors taking them. The parents can’t be there because they are at the doctor or the hospital.

What are some of the advancements that have happened in the care of patients with Dravet and what do you see for them in the future?

Dravet represents one of the best understood epilepsies since we know the genetic mutation that is the cause of the epilepsy. So that’s a really important thing. Understanding that has allowed us now to understand more about why it happens and hopefully get to a point where we understand how to treat it. People with other epilepsies or other genetic epilepsies should appreciate and support research that goes into Dravet syndrome because if you can figure out the genetic cause of one and figure out how to fix it, there’s a decent chance we might apply the same thoughts to other things and figure out how to cure other epilepsies down the road.

As far as big things that are going to come in the Dravet world … One thing is that pharmaceutical companies have increasingly recognized the importance of this syndrome, which is why you have multiple new pharmaceuticals being evaluated. Cannabidiol one. Fenfluramine, the other. Both trials we’re doing here. Some drugs being used in other syndromes are also being considered. The drug being used in muscular dystrophy that skips over the abnormality in the gene that causes the disorder to help make a more normal gene, they are looking at applying the same kinds of ideas in Dravet syndrome. If you could somehow skip over the abnormality in the SCN1A gene and make a more functional protein, might we be able to improve the disorder? Maybe? So those are some of the exciting things.

Several new drugs are probably going to be investigated in the future. They've got animal models that they can test drugs on to see which ones might be favorable and investigate it more. I mean who would have ever thought to look at fenfluramine. It was just part of a diet pill in the past. Somebody was smart enough to think, "Well maybe half that drug might be worth something. Let's go look at it." It appears to be very effective. At least in the open trials they've done.

What made you interested in Dravet Syndrome?

Really it was in training, in my residency ... I've always been fascinated with epilepsy and fascinated by the story of epilepsy. I've always been fascinated by the idea that the longer epilepsy goes on the more likely the story might actually be told. Which is why I always harp with my students that when you have a patient with intractable epilepsy, if you do not understand what's going on, you should always start from the beginning and work your way to the present because you might find a pattern and see the story as it's told over and over and over again.

Dravet is one of those things that tells a story over time. So in the beginning when it's just febrile seizures people might not quite put it together. But you take febrile seizures and then the types and how long they are and then put that you've got these new types of seizures. Now you've got developmental delay and EEG abnormalities, over time the story becomes clear.

I found so many cases of Dravet when I was in training in kids that were diagnosed with other things. There was a kid I remember when I was in training that was about to get epilepsy surgery, and this has actually happened multiple times since then, where I've seen people who were in the process of getting evaluated for epilepsy surgery and doctors are going over their history and trying to figure out if the patient was a surgical candidate. This kid sounds like he has Dravet syndrome. They are 14 or 15 years old and their family is wanting to do a surgery and then we find out, no they've got this underlying genetic epilepsy that is not surgically treatable. It's an important thing to figure out.

So over time I have encountered more and more kids with Dravet syndrome. We probably see somewhere between 40 and 50 patients. The longest distance someone came to see me was from Florida. There are a couple of spots in the US where Dravet syndrome is frequently treated and these typically develop from a doctor interested in the syndrome and word of mouth from the Dravet community. It's a very connected community. A group finds a doctor they like who understands what's going on, they share that with everybody and they end up all trying to go to the same place. It makes for a better clinic and better care when we can have that connection with our patients and they are connected with each other.

For more information:

• Jane and John Justin Neurosciences Center
• Dravet Syndrome treated at Cook Children's
• Cook Children's Comprehensive Epilepsy Program
• Contacts and Locations