Dravet Syndrome

Researchers are investigating ETX101, a gene therapy delivered via an adeno-associated viral vector, in infants and children diagnosed with SCN1A-positive Dravet syndrome. The study includes multiple age groups ranging from 6 months to under 18 years and aims to assess the safety and effects of ETX101. It is designed as a Phase 12, multicenter trial with different parts evaluating dose levels and treatment impact using a randomized, controlled approach in later stages. The study is divided into parts Part 1A uses an open-label, dose-escalation design to test up to four doses of ETX101 in participants aged 6 to under 36 months. Part 1B is open-label and tests a single dose in participants aged 48 months to under 18 years. Part 2 is a double-blind, randomized, sham delayed-treatment control study involving participants aged 6 to under 48 months, where participants receive either ETX101 or a sham procedure with delayed treatment. This part includes two cohorts and lasts up to 52 weeks. Participants will be closely monitored through the study with assessments of seizure frequency, cognitive and adaptive behavior changes using tools like the Bayley-4 and Vineland-3 scales, and clinical global impressions over 52 weeks. Safety and effectiveness are evaluated by comparing seizure counts before and after dosing. The study includes various cognitive and behavioral outcome measures and follows participants from dosing up to one year for treatment effects and safety observations.

Researchers are evaluating zorevunersen, an investigational antisense oligonucleotide drug, in children with Dravet syndrome, a rare and severe form of epilepsy. This Phase 3, global, multicenter, randomized, double-blind, sham-controlled study aims to assess the efficacy, safety, and tolerability of zorevunersen by measuring changes in major motor seizure frequency and other important aspects such as behavior, cognition, clinical status, and quality of life. Participants will be randomly assigned to receive either zorevunersen or a sham procedure during Treatment Period 1, which lasts about 52 weeks. Zorevunersen is given by intrathecal injection at specific doses and intervals throughout this period. After Treatment Period 1, all eligible patients enter Treatment Period 2, where everyone receives zorevunersen for additional dosing over several months. Patients who complete the study may have the chance to join an open-label extension to continue receiving the drug. During the study, participants will undergo regular assessments including seizure monitoring, behavioral and cognitive evaluations, and health-related quality of life measurements. The primary outcome is the change in major motor seizure frequency at Week 28, with secondary outcomes assessed at Week 52. Safety and tolerability are also closely monitored. Overall participation lasts through both treatment periods and possible extension, with detailed follow-up to evaluate the drugs potential for disease modification.

Researchers are developing a multicenter registry to collect and share data on pediatric patients who have undergone deep brain stimulation DBS for movement disorders such as dystonia, epilepsy, Tourette syndrome, and mood disorders. The study aims to improve understanding of DBS safety and effectiveness in children, as current data are limited and individual centers often have too few cases for strong research. This registry will support large-scale analyses and help refine DBS as a treatment option for hyperkinetic movement disorders in the pediatric population. The study involves gathering both retrospective and prospective clinical data from multiple pediatric centers. The registry will collect information on surgical techniques, patient outcomes, implant sites, and long-term effects of DBS. This collaborative data-sharing approach enables comprehensive evaluation of which patients benefit most from DBS and how it impacts their quality of life over time. Participants include children aged 0 to 18 years who have already received or are scheduled to receive DBS for neurological movement disorders. Data will be collected over five years to monitor safety, efficacy, and quality of life outcomes. The study does not involve treatment administration but focuses on gathering and analyzing clinical information. Parental or legal guardian consent is required for prospective participation.

Dravet Syndrome DS is a severe neurodevelopmental disorder caused mostly by mutations in the SCN1A gene, leading to frequent, drug-resistant seizures, cognitive deficits, and a high risk of sudden unexpected death in epilepsy SUDEP. SUDEP is a major cause of premature death in epilepsy patients and is linked to seizure frequency and brainstem dysfunction. This study aims to investigate serotonin 5HT pathway alterations in the brainstem of adults with DS using PET and MRI imaging to better understand SUDEP mechanisms. The study will include 20 adult participants 10 with confirmed Dravet Syndrome, 10 with drug-resistant focal epilepsy, and 10 healthy adults. All participants will undergo PET-MRI imaging with injection of the tracer 18F-MPPF to assess the serotonin brainstem pathway. The imaging involves anatomical MRI scans followed by a 90-minute dynamic emission scan after tracer injection. Women of childbearing potential will have a pregnancy test before imaging. Participants will have one inclusion visit for eligibility review and clinical examination, followed by the PET-MRI scan scheduled within 2 to 8 weeks. Researchers will compare brainstem serotonin receptor binding between groups and relate imaging findings to central sleep apnea duration and brainstem volume. The study will measure the signal-to-noise ratio of 5-HT1A receptor binding in healthy controls and monitor safety throughout. Each participants involvement lasts from 2 to 8 weeks.

Researchers are evaluating the drug LP352 in a phase 3, randomized, double-blind, placebo-controlled trial to study its effects on seizures in children and adults with Dravet Syndrome DS. This serious condition involves various seizure types with onset between 1 and 20 months of age. The study aims to test the efficacy, safety, and tolerability of LP352 compared to placebo over a total duration of about 24 months. Participants will be randomly assigned to receive either LP352 or a matching placebo. LP352 or placebo will be given orally or through a feeding tube. The study includes three main phases a Screening phase, a Titration period where doses are gradually increased to the highest tolerated level, and a Maintenance period to assess ongoing treatment effects. Afterward, participants will undergo a Taper period to reduce dosing and a Follow-Up phase for observation. During the study, participants will be monitored for seizure frequency changes, safety, and tolerability. Researchers will track countable motor seizures and measure percent change compared to baseline over up to 15 weeks. Participants or caregivers will complete seizure diaries, and stable antiseizure medication use is required. Safety evaluations will continue up to 21 weeks, with study visits scheduled throughout these phases. Total participation lasts approximately two years.

Researchers are investigating epilepsy-dyskinesia syndromes, which are rare genetic diseases causing both movement disorders and epilepsy in children. This multinational retrospective survey, supported by the International Parkinson and Movement Disorder Society, aims to collect detailed clinical and molecular data to better understand these conditions. The study focuses on identifying patterns in disease features, progression, and genetic links to improve knowledge and support precision medicine. The study collects previously recorded data from multiple countries, harmonizing information on clinical features, disease progression, age of onset, genetic variants, and coexisting neurological conditions. By standardizing this data, the survey addresses challenges in rare disease research like small, dispersed patient groups and inconsistent protocols. The goal is to build a shared clinical database and analyze how movement and seizure disorders relate at both clinical and molecular levels. Participants are children aged 0 to 18 years with diagnosed movement disorders linked to specific genetic variants. The study reviews existing medical records and genetic information without new treatments or interventions. Researchers will assess the disease spectrum, how movement disorders affect quality of life, and the effectiveness of symptomatic treatments over one year. The study encourages international collaboration to advance understanding and improve care for these rare conditions.

Researchers are evaluating clemizole hydrochloride EPX-100 as an additional treatment for children and adults with Dravet syndrome DS, a severe form of epilepsy. This Phase 3, multicenter, randomized, double-blind, placebo-controlled study aims to assess the safety and effectiveness of clemizole hydrochloride in reducing seizures. The study includes participants with confirmed DS who continue to have seizures despite other treatments and have a documented SCN1A genetic mutation. Participants first undergo a 4-week Observational Period to establish baseline seizure activity. Then, they enter a 16-week Double-Blind Period where they receive either clemizole hydrochloride or a placebo as an oral solution. Following this, eligible participants who complete the double-blind phase may continue to an Open-Label Extension Period, receiving clemizole hydrochloride for up to 3 years. During the study, participants are regularly monitored for changes in countable motor seizures per 28 days and other seizure-related outcomes. Assessments include clinical evaluations and seizure tracking, with safety monitored throughout the trial. The primary outcome focuses on seizure reduction over 16 weeks, while secondary outcomes evaluate seizure frequency, seizure-free days, and clinical impressions of improvement. Participants are followed for up to approximately 172 weeks, ensuring long-term safety and efficacy data are collected.

Researchers are evaluating the use of Pulsed Low-Intensity Focused Ultrasound PLIFU to reduce or suppress seizure activity in adults experiencing non-convulsive or focal motor status epilepticus SE who have not responded to standard treatments. The study focuses on brain regions that generate or control seizures, aiming to assess the effects of this non-invasive brain stimulation in a hospital setting. Participants will receive up to two sessions of PLIFU treatment in the Intensive Care Unit. Each session lasts 10 minutes and uses a custom device that delivers ultrasound to specific brain areas without damaging tissue. Treatments will be given after anti-seizure medications have been administered, and the ultrasound is applied using safe, non-thermal settings. During the study, participants will be monitored continuously with surface EEG to measure epileptic brain activity before, during, and after PLIFU treatment. Researchers will observe changes in seizure activity and follow participants throughout their hospital stay. The main outcome is the change in epileptiform activity measured by EEG at baseline and 10 minutes after treatment. The study aims to gather preliminary data to support future research.

Researchers are evaluating the safety and tolerability of ION337 in children aged 2 to 12 years with Dravet syndrome, a severe form of epilepsy. This open-label study is designed to assess how well participants tolerate this investigational drug and to monitor its effects over time. The study is led by Ionis Pharmaceuticals, Inc. and aims to gather detailed safety data in this pediatric population. Participants receive ION337 through an intrathecal bolus injection directly into the spinal fluid. The study has two parts Part 1 involves a 6-month period with a single ascending dose of ION337, where dosing levels increase sequentially. Participants who complete this phase may enter Part 2, which lasts 24 months and involves multiple ascending doses at the same dose level assigned in Part 1. After these treatment phases, there is a 7-month safety follow-up period to monitor participants. During the study, participants will be closely monitored for any treatment-emergent adverse events and changes in laboratory tests, vital signs, ECGs, physical and neurological exams, and suicidality assessments. Researchers will also measure ION337 concentrations in plasma and cerebrospinal fluid and track changes in seizure frequency. The total participation time can be up to 37 months, including treatment and follow-up, with regular study visits for assessments throughout the trial.

Researchers are studying patients with refractory or focal epilepsy who undergo pre-surgical evaluation using Stereoelectroencephalography SEEG. The goal is to create a detailed brain atlas of human cognition by collecting brain recordings taken during cognitive tasks performed as part of routine clinical care. This atlas will provide high temporal and spatial resolution data to better understand how epilepsy and epilepsy surgery affect cognitive functions. Participants will have intracerebral electrodes implanted as part of their invasive SEEG assessment to locate epileptogenic zones and evaluate cognitive risks before surgery. During this procedure, brain activity is recorded while patients perform cognitive tasks. This study uses Dynamic Spectral Imaging ISD to map gamma oscillations in the brain, which are linked to complex cognitive functions. Behavioral and neuropsychological data may also be collected after surgery. During the study, participants complete cognitive tasks while SEEG signals are visually and quantitatively analyzed over about three weeks. Researchers measure brain activity through functional mapping and record composite behavioral data. The study monitors patients intellectual capacity to comply with cognitive testing and collects detailed brain function data to improve understanding of epilepsys impact on cognition. Participation lasts through the clinical evaluation and data collection periods.