Dravet Syndrome

ENDEAVOR is a Phase 1/2, 2-part, multicenter study to evaluate the safety and efficacy of ETX101 in participants with SCN1A-positive Dravet syndrome aged ≥6 to \<36 months (Part 1A), aged ≥48 months to \<18 years (Part 1B), and aged ≥6 to \<48 months (Part 2). Part 1A follows an open-label, dose-escalation design, Part 1B follows an open-label design, and Part 2 is a randomized, double-blind, sham delayed-treatment control study.

Zorevunersen is an investigational new medicine for the treatment of Dravet syndrome. It is an antisense oligonucleotide (ASO) that is intended to increase the level of productive SCN1A messenger RNA (mRNA) and consequently increase the expression of the sodium channel Nav1.1 protein. This RNA-based approach is not gene therapy, but rather RNA modulation, as it does not manipulate nor insert genetic deoxyribonucleic acid (DNA). Zorevunersen is designed to upregulate Nav1.1 protein expression from the nonmutant (wild-type) copy of the SCN1A gene to restore physiological Nav1.1 levels. Nav1.1 levels are reduced in people with Dravet syndrome. This is a global, multicenter, randomized, double-blind, sham-controlled, parallel group Phase 3 study to assess the efficacy, safety, and tolerability of zorevunersen in patients with Dravet syndrome. The study duration and endpoints are designed to evaluate the potential of zorevunersen for disease modification. The study consists of two parts, Treatment Period 1 and Treatment Period 2. The primary and secondary endpoints will be assessed at the conclusion of Treatment Period 1. These endpoints will be assessed again at the end of Treatment Period 2. The primary endpoint is the change from baseline in major motor seizure frequency. Secondary endpoints include the change in behavior and cognition, clinical status, and health-related quality of life in patients with Dravet syndrome. Patients will have the opportunity to enroll in an open label extension study and receive zorevunersen if they meet eligibility criteria at the end of the study.

The use of deep brain stimulation (DBS) has expanded to include multiple conditions in children including dystonia, epilepsy, Tourette syndrome and mood disorders. Despite its growing application, DBS remains a low-volume procedure in most pediatric centers, which limits opportunities for large-scale research studies. To overcome this challenge, an international data-sharing platform is essential for advancing knowledge about DBS in pediatric patients, particularly concerning surgical techniques and patient outcomes across various conditions. This study aims to establish a multicenter pediatric DBS registry. With limited data on pediatric DBS outcomes and a small number of cases at individual centers, there is a need for a comprehensive registry to enable large-scale, well-powered analyses of DBS safety and effectiveness. The primary goals of this study are to: * Establish and implement a multi-center pediatric DBS registry * Facilitate large-scale analyses of DBS safety and effectiveness in children * Refine DBS as a treatment option for dystonia and other hyperkinetic movement disorders in children. Secondary objectives include: * Identifying which patients benefit most from DBS * Determining clinical variables that influence DBS responsiveness * Identifying optimal implant sites for specific conditions * Understanding the long-term effects of DBS in children * Assessing the impact of DBS on the quality of life in pediatric patients The study will involve both prospective and retrospective data collection from pediatric DBS patients.

This (DEEp SEA Study) is a double-blind, randomized, placebo-controlled, multicenter study to investigate the efficacy, safety, and tolerability of LP352 in the treatment of seizures in children and adults with DS. The study consists of 3 main phases: Screening, Titration period, and Maintenance period, followed by a Taper period and Follow-Up. Participants will be randomized to LP352 or placebo. The total duration of the study will be approximately 24 months.

Overview: The Epilepsy-Dyskinesia Study aims to advance the understanding of the clinical and molecular spectrum of epilepsy-dyskinesia syndromes, which are monogenic diseases causing both movement disorders and epilepsy. Design: Multinational Retrospective Survey: Survey Details: Endorsed by the International Parkinson and Movement Disorder Society, this multinational retrospective survey seeks to gather comprehensive data on: * Clinical Features and Progression: Examining developmental history and treatment responses. * Disease Aspects: Including the age of onset for movement disorders and seizures, genetic variants, and concurrent neurological conditions. Data Harmonization: By standardizing data collection across countries, the survey aims to overcome barriers in rare disease research and provide a unified understanding of these conditions. Study Aims: This study seeks to broaden our understanding of the spectrum and association of movement and seizure disorders through a retrospective review. By analyzing clinical data, the study aims to identify patterns and correlations between these conditions while investigating molecular data to uncover underlying genetic and biochemical mechanisms. The ultimate goal is to enhance knowledge of how these disorders interact and progress over time, offering new insights at both clinical and molecular levels. Overarching Goals: 1. Enhance understanding of movement disorders and epilepsy. 2. Inform precision medicine approaches. 3. Foster international collaboration for rare disease research.

This is a global, multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of clemizole hydrochloride as adjunctive therapy in children and adult participants with DS. The study consists of a 4-week Observational Period, a 16-week Double-Blind (DB) Period and an Open-Label Extension (OLE) Period for up to 156 weeks.

This study will consist of a Core Study, Extension Phase A and Extension Phase B. 1. Core Study will consist of the following 2 phases: Pretreatment (4 weeks screening or baseline period) and Treatment Period. The Treatment Period (23 weeks) of Core study include Titration period (10 weeks) and Maintenance period (13 weeks). 2. Extension Phase A will consist of a Treatment Period (33 weeks) and a Follow-up Period (4 weeks). All participants who will complete the Core Study will be eligible to participate in Extension Phase A of the study. 3. Extension Phase B will only be for participants who reside in countries where perampanel (oral tablets or oral suspension) is not commercially available or an extended access program (EAP) is not yet implemented, participants have completed Extension Phase A, and who, in the opinion of the investigator, will continue to benefit from treatment with perampanel.

This study proposes to sonicate epileptic zones or circuits at the bedside with a custom built PLIFU device in two groups of participants experiencing non-convulsive seizures while treated in the Intensive Care Unit (ICU): 1) non-convulsive SE or 2) focal motor Status Epilepticus (SE), targeting the thalami or motor cortical areas responsible for generating ictal activity, respectively. PLIFU modulation is non-ablative, nonionizing, and noninvasive, while it also preserves the integrity and function of brain tissue. The aim is to quantify ictal and interictal EEG before, during, and after sonication. Experiments will not alter the standard of care and only be implemented after antiseizure medications (ASMs) have been delivered to the patient. PLIFU sonication will be delivered to participants using burst tone and nonthermal parameters for 10 minute exposures. Hypothesis: PLIFU is a safe and non-invasive treatment that can reduce or suppress epileptic activity. The pilot data acquired is intended to be used as preliminary data for justifying a larger study. Recruitment was put on hold from Dec. 2023 to Oct. 2024 due to personnel changes and modifications to study needing approval.

The pre-surgical assessment of a cortectomy in patient suffering from a refractory epilepsy includes several examinations aiming both, to specify the epileptogenic zone (EZ) which must be resected and to evaluate functional and cognitive risks of surgery. Nevertheless, in some patients, non-invasive evaluation does not give formal answer. In these subjects, it is then necessary to carry out a second step, consisting of an invasive exploration by implantation of intracerebral electrodes during a Stereoelectroencephalography (SEEG). Due to its temporal and spatial resolution, the SEEG allows, besides the precise determination of the EZ, to carry out a functional mapping of the cortical regions likely to be included in cortectomy. Conventionally, this mapping is carried out on the basis of the cortical electrical stimulations applied to the implanted electrodes. If this approach is very robust for exploring primary functions such as motor skills or language, it cannot be used to evaluate more complex cognitive tasks such as face recognition or attention. Essential cognitive tasks on a daily basis. This has led to the development in recent years, in Grenoble, of a complementary approach to cerebral stimulation: Dynamic Spectral Imaging (ISD). Numerous experimental paradigms have demonstrated that the realization of a cognitive task associates with the generation within the cortical regions involved in its treatment of a particular cortical activity. This activity is characterized by oscillations of the cortical rhythm in high frequencies (\> 40 Hz), called gamma activities. The ISD thus consists in mapping this gamma activity during various cognitive tasks, thus making it possible to study more widely the complexity of the cognitive functions. MAPCOG\_SEEG aims to collect the cerebral recording of the patients who have performed this cognitive exploration to be able to in fine propose an Atlas of human cognition which takes advantage of the very rich information in terms of spatial and temporal resolution of the SEEG. Furthermore, it will exactly allow more to understand the impact of the epilepsy and the surgery of the epilepsy on the cognition.

The study is a pilot, open-label, study to test whether BMB-101 is safe and effective in reducing the frequency of seizures in subjects with Absence Epilepsy including Epilepsy with Eyelid Myoclonia (also called Jeavons Syndrome) as well as Developmental Epileptic Encephalopathies such as Dravet and Lennox Gastaut. The study will last up to 6 months. There will be a 1 month screening period, then up to 3 months on open-label BMB-101 including titration and tapering/washout periods, and then a 1 month follow-up period. There will be 6 clinic visits.