Dravet Syndrome Foundation attended the 2025 American Epilepsy Society (AES) Annual Meeting in Atlanta on December 5th -9th, where we participated and engaged in educational sessions, networked with clinicians and scientists, discussed important community priorities with industry partners, and assessed progress in the research landscape.
Dravet syndrome is a rare disease, and when DSF was established, it was still rarely mentioned, even at a conference focused on epilepsy. Looking back at 2009, there were only 10 abstracts (detailing a poster or presentation) that mention ‘Dravet,’ and there were no companies developing therapies for Dravet syndrome. In 2025, there were nearly 100 abstracts that included Dravet syndrome, and DSF met with more than ten pharmaceutical and biotechnology companies focusing on therapies for Dravet syndrome.
DSF Research Roundtable
For the 16th consecutive year, DSF hosted our Research Roundtable on Thursday evening, just before the AES meeting. What began in 2010 as a small, literal roundtable discussion bringing together a handful of advocates and scientists to review the state of research and develop a roadmap to a cure, has grown in 2025 to a major annual gathering filled with more than 180 experts, all deeply committed to advancing research, care, and treatment for Dravet syndrome. At the inaugural meeting, DSF had just awarded its very first research grant of $100,000; this year, DSF announced funding for 8 grant awards bringing our total research funding to an impressive $14.1 million across over 80 projects. Mary Anne Meskis, a founding family member and current DSF CEO, recently recalled the consensus at the first roundtable was that genetic therapies might one day be possible, but no one was expecting them to arrive within their lifetime. Sixteen years later, the lively discussions in the meeting room reflected the growing momentum in the field, including promising results from clinical studies actually testing genetically targeted therapies in patients with Dravet syndrome. This year’s Roundtable program began with a focus on the patient-family voice, featuring Nate and Whitney Batt sharing their family’s story and their Dravet-journey with their sons Cooper and Colton. The scientific portion of the program then proceeded with exciting research talks from DSF-funded researchers:
- Lori Isom, PhD (University of Michigan) spoke about her new rabbit model of Dravet syndrome that is enabling new insights into the relationships between cardiac function, seizures, and SUDEP risk;
- Satya Sahoo, PhD (Case Western University) and Jeffrey Buchhalter, MD, PhD (University of Calgary School of Medicine) revealed their progress developing an expert-informed AI-augmented knowledge platform for Dravet syndrome;
- Gaia Colsante, PhD (San Raffaele Scientific Institute) updated the audience on her work to genetically correct the SCN1A haploinsufficiency in targeted brain cells across different developmental time windows in a Dravet syndrome mouse model; and
- Sophie Hill, PhD (Children’s Hospital of Philadelphia) gave a comparative overview of the various genetic approaches to treating Dravet syndrome with a highlight of a research effort she has been working on in the Goldberg laboratory in collaboration with the Liu laboratory (Harvard) for a base-editing approach that has been successful in correcting the genetic mutation and symptoms in a mouse model of Dravet syndrome.
Major Advancements Toward Gene-Targeted Therapies and Disease Modification
Most patients with Dravet syndrome carry a mutation in the gene SCN1A, which holds the instructions to make an important sodium channel that is critical for the regulation of electrical activity in the brain. Mutations in SCN1A that cause Dravet syndrome result in about a 50% reduction of those sodium channels. Research has long focused on ways to boost expression of healthy SCN1A sodium channels to treat Dravet syndrome at the root cause and, hopefully, modify the full spectrum of disease symptoms. In recent years, scientific breakthroughs in gene-targeted therapies have provided enough evidence in animal and cell models to make the cross over into testing in human clinical studies. Two companies, Stoke Therapeutics and Encoded Therapeutics, have begun such studies and both were able to share updates on their data at this year’s meeting.
- In 2020, Stoke Therapeutics began Phase 1/2 studies of an antisense oligonucleotide called STK-001, now known as zorevunersen. Participants in these initial studies had the opportunity to transition into a long-term open-label extension study to continue to monitor the safety and efficacy of zorevunersen over time. Presentations at the 2025 AES Meeting detailed the findings from these studies, now with up to four years of data on some patients continuing to receive zorevunersen showing continued reduction of seizures as well as improvements in behavior, cognition, and quality of life. Furthermore, a new analysis of EEG data detected abnormalities across developmental ages in patients with Dravet syndrome that were improved following treatment with zorevunersen. Pivotal Phase 3 studies for zorevunersen are enrolling now: https://www.emperorstudy.com/
- In 2024, Encoded Therapeutics began Phase 1/2 studies of a one-time AAV9-based gene regulation therapy called ETX101. At AES, they revealed insights for the first time into initial safety and efficacy data from 19 participants that received a single intracerebroventricular injection of ETX101 at one of four dose levels. The safety data is favorable thus far; neurodevelopmental improvements were detected across the first three dose levels tested and substantial seizure reductions were reported at the third highest dose level (fourth dose level has not yet been analyzed for efficacy but is anticipated in 2026).
Conversations at AES around gene-targeted and disease-modifying therapies for Dravet syndrome extended beyond those two exciting clinical advancements. Indeed, work in animal models is exemplifying that there may be novel approaches to address Dravet syndrome in the future that may be able to expand upon the current state-of-the-art approaches being employed in clinical trials. Academic researchers, many of whom have been funded by DSF, detailed novel approaches to delivering a healthy copy of SCN1A, directly correcting the mutation within patient DNA, repairing the disrupted cellular networks in the brain, and investigating how symptoms are impacted when genetic approaches are utilized at varying timepoints. Additionally, companies such as Regel Therapeutics and RecoRNA Bio presented preclinical proof-of-concept data on genetic-based approaches for Dravet syndrome in their developmental pipeline.
Emerging Therapies and Ongoing Evidence for the Treatment of Dravet Syndrome
Dravet syndrome is within 5% of rare diseases that have an FDA-approved treatment; in fact, there are three anti-seizure medications approved specifically for Dravet syndrome: Fintepla (fenfluramine), Epidiolex (cannabidiol), and Diacomit (stiripentol). Three medications have undoubtably had a significant impact on patients, and even post-approval continued evidence is being gathered about their efficacy to reduce seizures, safety, and impacts on non-seizure symptoms like quality of life.
- Pharmaceutical-grade cannabidiol received FDA-approval for Dravet syndrome in 2018. This year, updates focused on understanding the real-world utilization of cannabidiol, indicating that introduction of cannabidiol was associated with reductions in polypharmacy and clinical visits, which could be reflective of reduced burden on patients.
- Stiripentol, approved in the US in 2018, has also continued to be a valuable therapeutic option for the treatment of seizure in Dravet syndrome. An international body of evidence continues to converge to confirm that stiripentol is an effective long-term treatment, and some reports this year also indicated an association with use of stiripentol and reduced rates of status epilepticus (form a 3-year post marketing surveillance study in Japan) and mortality (in a US-based cohort). However, some emerging studies suggest that stiripentol, as well as other Dravet-specific therapies, is being under-utilized in the treatment of Dravet syndrome. To address this, some efforts have been undertaken to understand some of the challenges to utilization of these therapies, including studies and information to better understand drug-drug interactions and development of expert consensus guidelines for use.
- For fenfluramine, which was originally approved in 2020, UCB presented final results with up-to four years of data on patients in their open-label extension study confirming the long-term efficacy for seizure reductions as well as improvements in global functioning without reports of any new safety or tolerability signals, and only 3% of patients (total of 265) with Dravet syndrome in the study discontinued treatment. These results were further supported by other smaller studies independently confirming the effectiveness of fenfluramine as a therapy in clinical practice for Dravet syndrome.
There was also a large showing of information on therapies all along the developmental pipeline from early testing in animal models to updates on ongoing clinical trials in patients.
- Neuromodulation is a topic of high interest in drug-resistance genetic epilepsies like Dravet syndrome; however, outside of Vagus Nerve Stimulation (VNS), little is known about the efficacy of neuromodulation approaches. Responsive Neurostimulation (RNS) involves an implantable device with electrodes that monitor brain activity and deliver specified, responsive electrical pulses. RNS has primarily been utilized in focal epilepsy, where the origin of seizure activity can be targeted. In generalized epilepsy, there may not be a specific location where seizures originate, making placement of the device less certain. However, a report at AES detailed case reports of 6 patients with Dravet syndrome between the ages of 6 and 21 years that had received RNS implantation. Four of the six patients responded with a significant reduction (>50%) in seizure frequency as well as reports of other quality of life improvements; the two non-responders also reported cognitive gains despite not reaching a 50% or greater seizure reduction. This early evidence suggests that RNS may be an effective and well-tolerated treatment approach for Dravet syndrome that warrants further study.
- Bexicaserin, previously known as LP352, is an investigational therapy for the treatment of seizures in developmental and epilepsy encephalophies (DEEs) like Dravet syndrome. Bexicaserin acts on the serotonin (5-HT) pathway by targeting activation of the 5-HT2C receptor. Previously developed by Longboard Pharmaceuticals, Lundbeck is sponsoring ongoing clinical studies of bexicaserin in children and adults with drug-resistance DEEs. Presentations at AES provided updates on their ongoing open-label and expanded access study arms with lasting effects on seizure reductions and continued positive reports of safety and tolerability. Phase 3 studies for bexicaserin are currently enrolling for patients with Dravet syndrome: https://deepdsstudy.com/
- Clemizole, also known as EPX-100, is an investigational therapy that targets 5-HT2 serotonin receptors. Clemizole was discovered as a potential antiseizure medication through drug screens in a zebrafish model of Dravet syndrome – studies that were originally supported by some of the first DSF grant awards. Harmony Biosciences presented new data from their open-label extension study of clemizole in patients with Dravet syndrome, with half of the patients in the study achieving a significant reduction in seizures. 24 patients in the study have continued into the extension phase, with favorable tolerability and safety data. The ARGUS Phase 3 trial continues to enroll for children and adults with Dravet syndrome: https://argustrial.com/
- Despite some prior promising work in mouse models investigating 4-phenylbutyrate (4-PBA), a report from Weill Cornell and Children’s Colorado detailed that only 1 out of 6 patients with Dravet syndrome experienced seizure reductions in a clinical pilot study, which is also lower than some of the other developmental epilepsy populations for which the therapy is being tested. While 4-PBA was generally well-tolerated, patients should be closely monitored for metabolic acidosis.
- Xenon Pharmaceuticals presented preclinical data on their compound, XPC-A, which selectively activates NaV1.1 sodium channels (encoded by the SCN1A gene). Treatment of a Dravet mouse model with XPC-A resulted in restoration of neuronal signaling, improved motor performance, reduced seizures, and protection from SUDEP.
- Preclinical assessment of relutrigine in zebrafish showed anticonvulsant potential similar to best-in-class current therapies for Dravet syndrome. Relutrigine is currently being tested by Praxis Medicines in clinical trials across developmental and epileptic encephalopathies, including Dravet syndrome: https://clinicaltrials.gov/study/NCT07010471
Breakthroughs in Academic Led Research
DSF has invested across the spectrum of topics in Dravet syndrome from early discovery of brain function to model system development to tracking the clinical picture of patients with Dravet syndrome. This broad approach acknowledges that early scientific discoveries in cell and animal models, as well as an understanding of the natural history of the disease, have laid the foundation for the development of transformational therapies. While therapeutic progress is bustling, academic research is still filling in the gaps to ensure that Dravet syndrome remains poised to benefit from new advancements in the therapeutic landscape. Over 14 presentations at this year’s meeting represented work stemming from DSF-funded projects, including updates from the SCN1A Horizon’s Study gathering prospective information on patients with SCN1A-related epilepsies across the UK; evaluation of novel approaches to behavioral profiling in Dravet-mice; elucidation of brain circuit functionality and the connection to therapeutic intervention and seizures; investigation of the impact of environmental factors on outcomes; and characterizing how cardiac function may be disrupted in Dravet syndrome. A poster from researchers heading the Dravet Genome Study at the Children’s Hospital of Philadelphia presented an update on their phenotypic reconstruction from the electronic health record of 100 patients with SCN1A-related epilepsy (representing 681 patient-years of information). You can learn more about their study and how to participate at this link. Other important work presented at AES this year included the expansion of clinical models and tools to study Dravet syndrome, the assessment of the role of novel cell types in the brain to the symptoms of Dravet syndrome, a deeper dive into understanding the functional effects of varied mutations in SCN1A, the investigation of disrupted circadian patterns and markers, and studies that seek to better understand mortality and SUDEP. This overview really is only able to scratch the surface of the diverse and detailed investigations into aspects of Dravet syndrome as research attempts to further close the gaps in our understanding.
Inclusion of the Patient Voice
DSF’s goal in attending AES has always been clear- to advocate for and support research that meets the needs of the patient community. A lot of focus is often poured into the research that must exist for the development of novel therapeutics. However, equally important is helping all the stakeholders – researchers, clinicians, pharmaceutical and biotechnology companies, government officials, and regulators – understand the lived experience of Dravet syndrome and the full spectrum of unmet needs for patients and their families. Several studies were presented this year focusing on the importance of diagnosis at any age, the burden of medical symptoms that go beyond just seizures on patients and their families, and the many ways that quality of life is impacted. In addition to the data that focused on those topics, DSF and patient families had the unique opportunity to bring some of the lived experience to life in rooms of professionals that are often laser focused on critical scientific and business barriers to therapy development. On Saturday, December 6th, caregiver and DSF Patient Advocacy Director Shannon Cloud, joined three clinicians to discuss the status of clinical care for patients with Dravet syndrome and where the field needs to improve outcomes for patients and their families in the CME accredited symposium, Striving for Excellence in Dravet Syndrome: Where We Are and Where We Need to Go. Next, on Sunday December 7th, a panel of 4 families to a loved one with Dravet syndrome joined DSF’s CEO Mary Anne Meskis and CSO Veronica Hood, PhD, along with Dr. Joseph Sullivan, to engage in a dialogue about the lived experience of Dravet syndrome and what we can learn from the past and current gaps in diagnosis and treatment. Both sessions allowed the audience to garner real insight into the challenges of Dravet syndrome as they are experienced by families on a day-to-day basis. Caregivers shared their stories with emotional impact that ensured the audience was not only incredibly moved but also engaged to act on the insights that were provided.
In reflecting on AES in 2025, particularly in the context of all the advancements that have happened in the last 16 years, I continue to be astounded at where the field is: the reality of gene therapies and disease modification in patients, the advancement of novel therapies, larger clinical data sets on patients than ever before, and cutting-edge exploration of deeper questions about the physiology underlying Dravet syndrome. So much of this began with the patient community, coming together and advocating, convening all the important stakeholders and building a foundation of research, all of which has coalesced into rapidly paced progress. There is still a lot of work to be accomplished, but it is encouraging to see how far we have come.
