Operational definition of developmental and epileptic encephalopathies to underpin the design of therapeutic trials

IF 6.6 1区医学 Q1 CLINICAL NEUROLOGY Epilepsia Pub Date : 2025-02-27 DOI:10.1111/epi.18265

Ingrid E. Scheffer, Jacqueline French, Kette D. Valente, Stéphane Auvin, J. Helen Cross, Nicola Specchio

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Abstract

Developmental and epileptic encephalopathies (DEEs) are the most severe group of epilepsies, characterized by drug-resistant seizures and developmental slowing or regression. DEEs encompass many epilepsy syndromes, although not all patients with a DEE can be classified into a specific syndrome. Our understanding of the etiologies of DEEs has been revolutionized with next-generation sequencing, with more than 900 genes implicated, in addition to structural causes. It is therefore now possible to consider precision medicine and novel therapeutic approaches for these devastating diseases with trials of repurposed and new drugs, including gene therapies. Trials are being designed to target either DEE diseases more broadly, specific DEE syndromes, or specific genetic DEEs. To serve this purpose, a clear operational definition of DEEs is needed to ensure that appropriate patients are selected for trials with precisely defined, targeted outcome measures. Herein we propose the operational definition of DEEs to set the stage for the development of DEE therapies.

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发育性和癫痫性脑病的操作定义，为治疗试验的设计提供依据。

发育性癫痫性脑病（DEEs）是最严重的一类癫痫，其特点是抗药性癫痫发作和发育迟缓或倒退。发育性癫痫包括多种癫痫综合征，但并非所有发育性癫痫患者都能归入一种特定的综合征。随着新一代测序技术的发展，我们对 DEE 病因的认识发生了革命性的变化，除了结构性原因外，还有 900 多个基因与之有关。因此，我们现在可以考虑采用精准医疗和新的治疗方法来治疗这些破坏性疾病，包括基因疗法在内的改用药物和新药试验。目前正在设计针对更广泛的 DEE 疾病、特定 DEE 综合征或特定遗传性 DEE 的试验。为此，需要对 DEE 进行明确的操作性定义，以确保选择合适的患者进行试验，并精确定义目标结果指标。在此，我们提出了 DEE 的操作定义，为 DEE 治疗方法的开发奠定基础。

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来源期刊

Epilepsia 医学-临床神经学

CiteScore

10.90

自引率

10.70%

发文量

319

审稿时长

2-4 weeks

期刊介绍： Epilepsia is the leading, authoritative source for innovative clinical and basic science research for all aspects of epilepsy and seizures. In addition, Epilepsia publishes critical reviews, opinion pieces, and guidelines that foster understanding and aim to improve the diagnosis and treatment of people with seizures and epilepsy.