Dravet Syndrome (DS)

The goal of this clinical trial is to learn the best way to switch children with Lennox-Gastaut Syndrome (LGS) or Dravet Syndrome (DS) taking 'artisanal' (non pharmaceutical-grade) cannabidiol (CBD) to Epidiolex for treatment of seizures. The main questions it aims to answer are: * How well does a gradual switch from 'artisanal' CBD to Epidiolex work? * Does the same dose of Epidiolex as 'artisanal' CBD work best? * What side-effects or medical problems do participants have when switching from 'artisanal' CBD to Epidiolex? Researchers will examine how successful switching from 'artisanal' CBD to Epidiolex is. Participants will: * Gradually increase their dose of Epidiolex and reduce their dose of 'artisanal' CBD until they are taking just Epidiolex * Visit the clinic five times over 20 weeks for checkups and tests * Keep a diary of their seizures, symptoms and the number of times they use a rescue seizure medication

Dravet syndrome (DS) is a developmental and epileptic encephalopathy, usually caused by de novo pathogenic SCN1A variants, characterized by early-onset prolonged febrile seizures, subsequent drug-resistant polymorphic epilepsy, developmental impairment, and, in some patients, progressive motor, cognitive and behavioral decline. Despite the expanding therapeutic landscape, objective biomarkers for disease stratification, monitoring and treatment response are lacking. Blood-based markers of neurodegeneration, synaptic plasticity and neuroinflammation are promising candidates because they are minimally invasive and may capture biological processes involved in disease progression. TEMBO-DS is a prospective multicenter observational pilot study enrolling 60 individuals with DS and 30 age- and sex-matched healthy controls. DS participants will carry pathogenic or likely pathogenic SCN1A variants and fulfill ILAE clinical criteria, with no age limits. Individuals with epileptic spasms, SCN1A gain-of-function encephalopathy, structural causes of epilepsy, or systemic, oncological, autoimmune or neurodegenerative conditions potentially affecting biomarker levels will be excluded. At baseline, demographic and clinical variables will be collected, including age at seizure onset, seizure type and frequency, status epilepticus, SCN1A variant type, cognitive, motor, behavioral and sleep profiles, comorbidities and ongoing treatments. Blood samples obtained during routine clinical sampling will be analyzed for biomarkers of neurodegeneration and glial injury (NfL, GFAP, tau-related markers), synaptic plasticity (BDNF) and neuroinflammation. In a subgroup of DS participants, clinical assessment and blood sampling will be repeated after approximately 12 months. The study will assess whether biomarker levels differ between DS and controls and whether they correlate with clinically relevant measures of disease severity and longitudinal change. Particular emphasis will be placed on the relationship between NfL and Vineland adaptive functioning, including their changes over 12 months and the effect of treatment modifications. Group comparisons, correlation analyses and longitudinal mixed-effects models will be used, with adjustment for relevant covariates and multiple testing. The study is expected to identify one or more blood-based biomarkers, or biomarker combinations, associated with DS, disease severity and clinical evolution. These findings may provide objective measures for future natural-history studies and therapeutic trials, including the assessment of non-seizure outcomes.

This is an open-label, single-center study to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of intrathecal RC001 in patients with Dravet syndrome aged 2 to 18 years. The study includes a dose-escalation part followed by a fixed dose treatment part, with participant progression based on investigator-assessed safety and efficacy.

Dravet syndrome is a genetic epilepsy associated with pathogenic variants in SCN1A that codes for Nav1.1, a protein necessary for sodium channels. Children with Dravet syndrome classically present in the first year of life with prolonged seizures, often hemiclonic and in the setting of fever or temperature changes such as getting in or out of bath water. Many anti-seizure medications are sodium channel blockers and exacerbate seizures in this patient population. This creates some limitations in medication choices for this patient population. Recently fenfluramine was approved for use in Dravet syndrome for people 2 years and older. Randomized studies demonstrated a 74.9% reduction of convulsive motor seizures compared to 19.2% in the placebo group. Additionally, 16% of children treated with fenfluramine were seizure free. Fenfluramine is likely to be as effective in children under the age of 2 years. The current study has proposed an intermediate size patient population expanded access protocol to allow access to fenfluramine for children under 24 months of age.

This study is a preliminary open-label, single-arm Phase II investigation into the safety and efficacy of transdermal cannabidiol (CBD) delivered using GT4 skin bream technology in individuals diagnosed with Dravet and/or Lennox-Gastatu syndrome (DS and/or LGS). We aim to enroll 25 participants between the ages of 2 and 55 diagnosed with DS and/or LGS. Transdermal delivery of cannabinoids may provide advantages over other traditional routes of administration. Noted advantages include avoidance of first pass metabolism which mitigates potentially dangerous drug-drug interactions due to delayed cannabinoid accumulation, and more stable and constant plasma cannabinoid concentrations. GT4 technology, uses emulsion technology containing penetrating agents, basement membrane disruptors, and vasodilators to overcome hydrophilic and lipophilic structures to open channels and transport cannabinoids deep into the dermis layer of the skin. Once in the dermis, vasodilators dilate the capillary bed to increase fluid dynamic flow into and out of the application site, delivering cannabinoids into the blood stream. The primary objective is to investigate the safety and efficacy of CBD delivery with the A-Synaptic GT4 Transdermal Delivery System in individuals diagnosed with DS and/orLGS. Dr. Rotenberg will apply for and hold the expanded access IND for this study, as the sponsor is running this study as an investigator-initiated study. The study consists of 11 visits over \~160 days, dosing begins at Visit #2.