Evidence map›Paper›PMID 40024627›Full record

ArticleJournal of inherited metabolic disease2025

Spermidine Treatment Improves GRIN2B Loss-Of-Function, A Primary Disorder of Glutamatergic Neurotransmission.

A Santos-Gómez, N Juliá-Palacios, A Rejano-Bosch, R Marí-Vico, F Miguez-Cabello, M Masana, D Soto, M Olivella, À García-Cazorla, X Altafaj

Abstract read
In one paragraph

Article in Journal of inherited metabolic disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
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

10 authors.

A Santos-GómezDepartment of Biomedicine, School of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona, Barcelona, Spain.
N Juliá-PalaciosNeurometabolic Unit, Department of Neurology, Hospital Sant Joan de Déu-CIBERER, Barcelona, Spain.
A Rejano-BoschDepartment of Biomedicine, School of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona, Barcelona, Spain.
R Marí-VicoNeurometabolic Unit, Department of Neurology, Hospital Sant Joan de Déu-CIBERER, Barcelona, Spain.
F Miguez-CabelloDepartment of Biomedicine, School of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona, Barcelona, Spain.
M MasanaDepartment of Biomedicine, School of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona, Barcelona, Spain.
D SotoDepartment of Biomedicine, School of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona, Barcelona, Spain.
M OlivellaBioinformatics and Medical Statistics Group, University of Vic-Central University of Catalonia, Vic, Spain.
À García-CazorlaNeurometabolic Unit, Department of Neurology, Hospital Sant Joan de Déu-CIBERER, Barcelona, Spain.
X AltafajDepartment of Biomedicine, School of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona, Barcelona, Spain.

Funding

Fundació la Marató de TV3 607/C/2022Instituto de Salud Carlos III FI21/00073Instituto de Salud Carlos III PI19/00348Instituto de Salud Carlos III PI22/00515Ministerio de Economia y Competitividad CEX2021-001159Ministerio de Economia y Competitividad PID2020-119932GB-I00Ministerio de Economia y Competitividad PID2021-124896OA-I00
6 · The paper itself

Abstract

GRIN-related disorders (GRD) developmental and epileptic encephalopathies (DEEs) display a clinical spectrum including developmental delay, hypotonia, intellectual disability, epilepsy, and autistic traits. The presence of de novo pathogenic variants in the GRIN genes alters the N-methyl D-aspartate receptor (NMDAR) function, with a genotype-phenotype relationship. Despite recent advances to elucidate GRD pathophysiological mechanisms and to find treatments, to date, GRD therapeutic arms are still scarce and with limited efficacy. Herein, we investigated whether the natural polyamine spermine-positive allosteric modulators of GluN2B subunit-containing NMDARs-or its precursor spermidine might rescue NMDAR hypofunctionality. In heterologous cell systems, administration of spermine potentiated wild-type and loss-of-function (LoF) NMDAR-mediated currents and attenuated synaptic density deficits. Functionally, the putative therapeutic benefit of spermidine (spermine precursor) was assessed in constitutive Grin2b

Indexed as

Receptors, N-Methyl-D-AspartateSpermidineSynaptic TransmissionAnimalsDisease Models, AnimalFemaleHippocampusHumansLoss of Function MutationMaleMiceSpermineNR2B NMDA receptorReceptors, N-Methyl-D-AspartateSpermidineSperminedevelopmental encephalopathiesglutamatergic neurotransmissionmetabolic treatmentNMDA receptorprecision medicinespermidine

Identifiers

PMID40024627
PMCPMC11872566

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

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.