Phenylbutyrate for monogenetic epilepsy: Literature review

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research Pub Date : 2025-07-01 DOI:10.1016/j.eplepsyres.2025.107621

Amelia Stone , Jacqueline Burré , Natalie Wayland , Zachary M. Grinspan

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引用次数: 0

Abstract

Monogenetic epilepsies are seizure disorders with a single-gene etiology. More than 500 genes are linked to epilepsy. As many as 40 % of epilepsies are caused by variants in one of these genes. Single gene-linked epilepsies have a wide phenotypic spectrum and may be accompanied by comorbidities such as developmental and motor delays. Epilepsy is often pharmacoresistant and does not respond to existing drug therapies. Preclinical data suggests that 4-phenylbutyrate (PBA) may produce an anti-seizure effect in individuals with genetic epilepsies, including STXBP1, SLC6A1, SLC6A8, GABA(A) disorders, Dravet Syndrome (SCN1A), and LGI1 variants. Clinical data also suggests that PBA may have a therapeutic effect for SYNGAP1. This literature review describes the clinical profiles of several monogenetic epilepsies and the pathogenesis of seizure activity in these disorders. We focus on gene-linked epilepsy syndromes that may benefit from treatment with PBA according to several proposed theories of the drug’s mechanism and functional impact.

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苯丁酸酯治疗单基因癫痫：文献综述

单基因癫痫是具有单基因病因的癫痫性疾病。超过500个基因与癫痫有关。高达40% %的癫痫是由这些基因中的一种变异引起的。单基因关联癫痫具有广泛的表型谱，并可能伴有合并症，如发育和运动迟缓。癫痫通常是耐药的，对现有的药物治疗没有反应。临床前数据表明，4-苯基丁酸（PBA）可能对遗传性癫痫患者产生抗癫痫作用，包括STXBP1、SLC6A1、SLC6A8、GABA(A)障碍、Dravet综合征（SCN1A）和LGI1变体。临床数据也表明PBA可能对SYNGAP1有治疗作用。这篇文献综述描述了几种单基因癫痫的临床概况和这些疾病的发作活动的发病机制。根据PBA药物作用机制和功能影响的几种理论，我们将重点关注基因相关癫痫综合征，这些综合征可能受益于PBA治疗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Epilepsy Research 医学-临床神经学

CiteScore

0.10

自引率

4.50%

发文量

143

审稿时长

62 days

期刊介绍： Epilepsy Research provides for publication of high quality articles in both basic and clinical epilepsy research, with a special emphasis on translational research that ultimately relates to epilepsy as a human condition. The journal is intended to provide a forum for reporting the best and most rigorous epilepsy research from all disciplines ranging from biophysics and molecular biology to epidemiological and psychosocial research. As such the journal will publish original papers relevant to epilepsy from any scientific discipline and also studies of a multidisciplinary nature. Clinical and experimental research papers adopting fresh conceptual approaches to the study of epilepsy and its treatment are encouraged. The overriding criteria for publication are novelty, significant clinical or experimental relevance, and interest to a multidisciplinary audience in the broad arena of epilepsy. Review articles focused on any topic of epilepsy research will also be considered, but only if they present an exceptionally clear synthesis of current knowledge and future directions of a research area, based on a critical assessment of the available data or on hypotheses that are likely to stimulate more critical thinking and further advances in an area of epilepsy research.