ドラベ症候群

This article summarizes data for 13 investigational treatments for which at least preliminary seizure outcome data in patients with epilepsy were reported at the Eighteenth Eilat Conference on New Antiepileptic Drugs and Devices held in Madrid, Spain, on May 3-6, 2026. The treatments reviewed include bexicaserin, a selective 5-hydroxytryptamine (5-HT, serotonin) type 2C (5-HT2C) receptor superagonist investigated as a treatment for developmental and epileptic encephalopathies (DEEs); BMB-101, a selective 5-HT2C receptor agonist investigated for the treatment of absence seizures and DEEs; elsunersen, an antisense oligonucleotide designed for the treatment of early-onset SCN2A-DEE; EPX-100 (clemizole hydrochloride), an antihistamine endowed with agonist activity at 5-HT2A and 5-HT2B receptors, repurposed as a treatment for DEEs; ES-481, an antagonist of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors containing the transmembrane AMPA receptor regulatory protein γ8 (TARP-γ8), under investigation for the treatment of drug-resistant epilepsy; ETX-101, a gene therapy in development for the treatment of SCN1A-positive Dravet syndrome; PrevEp-006 (intranasal seletracetam), a synaptic vesicle glycoprotein 2A (SV2A) ligand under investigation as an acute seizure rescue therapy; radiprodil, a negative allosteric modulator that binds to the GluN2B subunit of the N-methyl-D-aspartate (NMDA) receptor, in development for the treatment of seizures and other symptoms associated with GRIN-related neurodevelopmental disorder, tuberous sclerosis complex, and focal cortical dysplasia type II; RAP-219, a selective negative allosteric modulator of TARP-γ8, in development for drug-resistant focal epilepsy; relutrigine, a selective disease-state sodium channel modulator investigated as a treatment for SCN2A- and SCN8A-DEE; Staccato Alprazolam, a breath-actuated device that delivers alprazolam to the lungs for rapid seizure termination; vormatrigine, a functionally selective sodium channel modulator in development for the treatment of focal seizures; and zorevunersen, an antisense oligonucleotide engineered to restore endogenous Nav1.1 protein expression, investigated for the treatment of Dravet syndrome. Overall, the evidence reviewed justifies expectations for improved health outcomes for the millions of children and adults with epilepsy who do not fully benefit from existing therapies.

PURPOSE: This multinational survey explored caregivers' preferences and training needs regarding the administration of rescue medication for prolonged convulsive seizures in children and adolescents with epilepsy across 7 European countries. METHODS: A total of 68 caregivers of children with epilepsy (aged 6 months to 18 years) who had experienced a prolonged convulsive seizure in the past 12 months completed an anonymous survey in 2024. The survey assessed caregiver preferences and satisfaction with buccal, nasal, or rectal rescue medication, quality of life (QoL), valued medication attributes, and training experience. Intranasal formulations were not consistently available across countries during the study period. RESULTS: Most caregivers (80.9%) preferred buccal over rectal or nasal administration, and satisfaction was higher among users of buccal midazolam compared with rectal diazepam. This preference aligned with a positive impact on patients' and caregivers' QoL. Caregivers rated ease of administration as the most important attribute of rescue medication (mean: 4.8/5), followed by effectiveness in stopping seizures (mean: 4.1/5). Despite their critical role, 44.1% had received no specific training; among those trained, 62.2% preferred face-to-face sessions. Training satisfaction was higher among caregivers who administered buccal midazolam (mean: 8.3/10; standard deviation [SD]: 2.4) compared with those using rectal diazepam (mean: 5.3/10; SD: 3.3). CONCLUSION: This survey underscores a strong caregiver preference for buccal midazolam in pediatric out-of-hospital settings. However, caregiver training remains a substantial unmet need, and standardized programs could improve preparedness for managing prolonged seizures. These findings reinforce the importance of integrating caregiver perspectives to optimize emergency pediatric epilepsy care.

Lafora disease (LD) is a fatal neurodegenerative disorder caused by mutations in the EPM2A or EPM2B/NHLRC1 genes, encoding Laforin and Malin, respectively. While the Laforin/Malin E3-ubiquitin ligase complex is a known regulator of canonical autophagy and glycogen metabolism, its role in non-canonical autophagy pathways remains unexplored. Given that neuroinflammation is a hallmark of LD, we investigated the relationship between the Laforin/Malin complex and Rubicon, a critical regulator of LC3-associated phagocytosis (LAP) and LC3-associated endocytosis (LANDO). In this work, we identify Rubicon as a novel substrate and binding partner of the Laforin/Malin complex. Co-immunoprecipitation and confocal microscopy assays in HEK293 and U2OS cells demonstrated that Malin physically interacts with Rubicon, promoting its K63-linked polyubiquitination. This post-translational modification adds another layer of control to the regulation of Rubicon in specific cellular contexts. To determine the functional relevance of this interaction in LD, we assessed LAP and LANDO in primary astrocytes from Malin-deficient mice. Using flow cytometry, we quantified the engulfment and degradation of Zymosan particles and microglial debris (LAP), as well as EGF receptor internalization (LANDO). Surprisingly, no significant functional impairments were observed in Malin-deficient astrocytes compared to WT controls. These findings suggest that while the Laforin/Malin complex regulates Rubicon via K63-linked ubiquitination, redundant signaling nodes may preserve non-canonical autophagy output in Malin-deficient astrocytes.

Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy caused by SCN1A haploinsufficiency. While brain pathology has been extensively studied, the retina remains underexplored. This study investigated retinal structural, functional, vascular, and cellular changes in a Scn1a+/- rat model of DS. Anatomical quantification revealed thinning of the retinal nerve fiber layer and thickening of the outer plexiform layer. Electroretinography (ERG) showed selectively reduced oscillatory potential amplitudes, suggesting dysfunction of neurovascular coupling. Consistent with these findings, immunohistochemistry demonstrated aberrant vascular morphology, including increased vessel curvature and reduced branching density. In addition, we observed robust microglial activation in the outer and inner plexiform layers; however, astrocyte morphology remained largely unchanged. Fenfluramine, an approved anti-seizure drug for DS, attenuated microglial activation but failed to rescue retinal structural or vascular deficits, indicating a dissociation between its anti-inflammatory and disease-modifying effects. Our findings suggest that multimodal retinal assessment could serve as a noninvasive biomarker platform for monitoring disease progression and therapeutic response in DS.

Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy whose clinical and research representation requires integration of heterogeneous knowledge spanning seizures, development, behavior, SUDEP/autonomic risk, genetics, comorbidities, electrophysiology, pharmacology, and drug responsiveness. We report the development of a DS-focused ontology created by expert-guided specialization of a previously published epilepsy ontology. Scope expansion was defined through a scientific advisory board, structured review meetings, and iterative ontology curation in OWL. The resulting resource reorganized DS content across nine major domains and expanded the publicly released ontology from the pre-extension baseline to the current BioPortal version. Beyond structural growth, the ontology was assessed through expert-guided curation and downstream task-based reuse, including two published ontology-enabled LLM studies and an ongoing ontology-derived DS knowledge graph and AI assistant platform. These results suggest that disease-focused ontology specialization can provide durable infrastructure for DS data harmonization, knowledge representation, and AI-enabled translational informatics.