畸形神经元消融是一种安全有效的治疗局灶性皮质发育不良II的方法。

IF 12 1区 医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Ying Xu, Jun Li, Zihao Wang, Rongrong Lu, Yingying Liu, Min Wang, Hao Li, Rui Zhao, Weijun Feng
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引用次数: 0

摘要

局灶性皮质发育不良II型(FCD II)是儿童难治性癫痫的主要原因,但治疗选择仍然有限。FCD II最常见的遗传原因是PI3K-AKT-mTOR通路基因的镶嵌和体细胞变异,导致mTOR信号的过度激活。由mTOR信号过度活跃引起的畸形神经元(dn)的存在对于FCD II型癫痫的发展至关重要。FCD II的一个关键治疗挑战和机遇是选择性地消除DNs。在这里,我们在FCD II小鼠模型中开发了两种特异性消融DN的策略,结果表明,DN消融足以预防和消除小鼠癫痫。此外,相关的神经行为异常也在治疗后得到逆转。因此,我们的研究提供了概念验证证据,证明DN消融是未来治疗FCD II的一种非常有前途的方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Ablation of dysmorphic neurons is a safe and effective treatment for focal cortical dysplasia II.

Focal cortical dysplasia type II (FCDII) is a leading cause of refractory epilepsy in children, yet treatment options remain limited. The most frequent genetic cause of FCDII is mosaic and somatic variants in genes of the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) pathway, leading to hyperactivation of mTOR signaling. The presence of dysmorphic neurons (DNs) resulting from hyperactive mTOR signaling is critical for the development of epilepsy in FCDII. One critical therapeutic challenge and opportunity for FCDII is to selectively eliminate DNs. Here, we developed two strategies to specifically ablate DNs in FCDII mouse models, and the results demonstrate that DN ablation is sufficient to both prevent and eliminate epilepsy in mice. Moreover, the associated neurobehavioral abnormalities were also reversed following treatment. Therefore, our study provides proof-of-concept evidence that DN ablation is a highly promising approach for curing FCDII in the future.

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来源期刊
Molecular Therapy
Molecular Therapy 医学-生物工程与应用微生物
CiteScore
19.20
自引率
3.20%
发文量
357
审稿时长
3 months
期刊介绍: Molecular Therapy is the leading journal for research in gene transfer, vector development, stem cell manipulation, and therapeutic interventions. It covers a broad spectrum of topics including genetic and acquired disease correction, vaccine development, pre-clinical validation, safety/efficacy studies, and clinical trials. With a focus on advancing genetics, medicine, and biotechnology, Molecular Therapy publishes peer-reviewed research, reviews, and commentaries to showcase the latest advancements in the field. With an impressive impact factor of 12.4 in 2022, it continues to attract top-tier contributions.
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