Evidence map›Paper›PMID 42754728›Full record

ArticleNature medicine2026

Levetiracetam therapeutically targets GABAergic synapses in diffuse midline glioma.

Tara Barron, Richard Drexler, Aaron Mochizuki, Evan Cantor, Kiarash Shamardani, Pamelyn J Woo, Neeraj Soni, Dana Tlais, Andrea Franson, Samantha Lyons and 22 more

Abstract read
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In one paragraph

Article in Nature medicine, 2026. 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
–field-weighted citation impact
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

32 authors.

Tara BarronDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.
Richard DrexlerDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.
Aaron MochizukiDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-1073-916X
Evan CantorDepartment of Pediatric Hematology/Oncology, University of Michigan, Ann Arbor, MI, USA.
Kiarash ShamardaniDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-2548-705X
Pamelyn J WooDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.
Neeraj SoniDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-4191-6723
Dana TlaisDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.
Andrea FransonDepartment of Pediatric Hematology/Oncology, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-5361-7683
Samantha LyonsDepartment of Pediatric Hematology/Oncology, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0001-7652-188X
Truman KnowlesUniversity of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0009-0002-9501-823X
Shannon RaberUniversity of California, San Francisco, San Francisco, CA, USA.
Vilina MehtaDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.
Michael A QuezadaDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-7307-5204
Michael B KeoughDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.
Samin Malaki JahanDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0009-0008-0200-1310
Linh Thuy VoDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.
Enrique Herrera CastañedaDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.
Kathryn R TaylorDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.
Lijun NiDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.
Kim KilianDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0009-0002-5827-7152
Samuel H WuDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.
Franz L RicklefsDepartment of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.ORCID http://orcid.org/0000-0002-1321-6930
Ulrich SchüllerInstitute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.ORCID http://orcid.org/0000-0002-8731-1121
Sabine MuellerUniversity of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-8216-9357
Paul G FisherDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-1196-1590
Cynthia J CampenDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-3519-1375
Hannes VogelDepartment of Pathology, Stanford University, Stanford, CA, USA.
Sonia PartapDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-5615-7689
Kai KailaFaculty of Bio- and Environmental Sciences (MIBS), University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0003-0668-5955
Carl KoschmannDepartment of Pediatric Hematology/Oncology, University of Michigan, Ann Arbor, MI, USA.
Michelle MonjeDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA. mmonje@stanford.edu.ORCID http://orcid.org/0000-0002-3547-237X

Funding

Targeting the Vasular SystemP50CA165962 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Benjamin Harris Kann · 2013 to 2026
$33.5M
Targeting the neuronal microenvironment in glioblastomaU19CA264504 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI Tracy T Batchelor · 2021 to 2026
$6.4M
Glioma Circuitry: Bridging Systems Neuroscience and CancerDP1NS111132 · NINDS · STANFORD UNIVERSITY · PI MONJE-DEISSEROTH, MICHELLE · 2018 to 2022
$5.7M
Neuronal Regulation of Low-Grade GliomagenesisR01CA258384 · NCI · STANFORD UNIVERSITY · PI David H Gutmann, Michelle Monje-Deisseroth · 2022 to 2026
$3.1M
Cancer Prevention and Research Institute of Texas (Cancer Prevention Research Institute of Texas) RR250137NCI NIH HHS P50 CA165962NCI NIH HHS R01 CA258384NCI NIH HHS U19 CA264504NINDS NIH HHS DP1 NS111132U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA258384U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) U19CA264504
6 · The paper itself

Abstract

Antiseizure medications, such as levetiracetam, are commonly used in glioma patients. Retrospective analyses evaluating effects of antiseizure medications on glioma patient survival have yielded inconsistent results, probably due to confounding factors of glioma subtype and drug class. Here we present retrospective real-world clinical data that demonstrate longer overall survival for children with diffuse midline glioma (DMG) who were taking levetiracetam, which was not evident in pediatric patients with hemispheric high-grade glioma. In preclinical models, levetiracetam reduces glioma proliferation and tumor burden, extending survival of mice bearing DMG orthotopic xenografts. These beneficial effects were not found in hemispheric high-grade glioma patient-derived orthotopic xenograft models. The subtype-specificity of this antiproliferative effect of levetiracetam is congruent with recent findings that GABAergic neuron-to-glioma synapses promote glioma growth in DMG but not hemispheric high-grade glioma. We demonstrate here that levetiracetam attenuates low-frequency GABAergic synaptic transmission in a glioma-specific manner, reducing GABAergic synaptic currents in DMG but not in healthy neurons. This effect is independent of action on SV2A, the chief mechanism by which levetiracetam functions to prevent and treat seizures. Taken together, these findings indicate a promising approach to target GABAergic synapses in DMG and suggest that use of levetiracetam in DMG should be further studied in future prospective clinical studies.

Identifiers

PMID42754728

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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 OpenQuestion graph.