Evidence map›Paper›PMID 40437754›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025

Ablation of dysmorphic neurons is a safe and effective treatment for focal cortical dysplasia II.

Ying Xu, Jun Li, Zihao Wang, Rongrong Lu, Yingying Liu, Min Wang, Hao Li, Rui Zhao, Weijun Feng

Abstract read
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In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Ying XuInstitute of Pediatrics, Children's Hospital of Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
Jun LiInstitute of Pediatrics, Children's Hospital of Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
Zihao WangInstitute of Pediatrics, Children's Hospital of Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
Rongrong LuDepartment of Neurosurgery, Children's Hospital of Fudan University, National Children's Medical Center (Shanghai), Shanghai 201102, China.
Yingying LiuInstitute of Pediatrics, Children's Hospital of Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
Min WangDepartment of Neurosurgery, Children's Hospital of Fudan University, National Children's Medical Center (Shanghai), Shanghai 201102, China.
Hao LiDepartment of Neurosurgery, Children's Hospital of Fudan University, National Children's Medical Center (Shanghai), Shanghai 201102, China.
Rui ZhaoShanghai Children's Hospital, School of medicine, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: dr_zhaorui@sina.com.
Weijun FengInstitute of Pediatrics, Children's Hospital of Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China. Electronic address: fengweijun@fudan.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

Ablation TechniquesDiphtheria ToxinEpilepsyGene EditingHeparin-binding EGF-like Growth FactorMalformations of Cortical Development, Group INeuronsAnimalsCRISPR-Cas SystemsDisease Models, AnimalHEK293 CellsHumansMiceProto-Oncogene Proteins c-aktTOR Serine-Threonine KinasesDiphtheria ToxinHeparin-binding EGF-like Growth FactormTOR protein, mouseProto-Oncogene Proteins c-aktTOR Serine-Threonine Kinasescell ablationDNsDTR/DTdysmorphic neuronsFCDIIfocal cortical dysplasia type IIgenetic epilepsy

Identifiers

PMID40437754
PMCPMC12432865

What Socratic holds

Textmetadata
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.