Evidence map›Paper›PMID 37780204›Full record

ArticleFrontiers in cellular neuroscience2023

NADPH oxidase 4 inhibition is a complementary therapeutic strategy for spinal muscular atrophy.

Mirella El Khoury, Olivier Biondi, Gaelle Bruneteau, Delphine Sapaly, Sabrina Bendris, Cynthia Bezier, Zoé Clerc, Elias Abi Akar, Laure Weill, Assaad A Eid and 1 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Frontiers in cellular neuroscience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.6field-weighted citation impact, top 26% of its field
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

1 citing paper in PubMed, 2 citations in OpenAlex.

  1. Review
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

11 authors at 4 institutions in 2 countries.

Mirella El KhouryFaculty of Basic and Biomedical Sciences, University Paris Cité & Inserm UMR_S1124, Paris, France.
Olivier BiondiFaculty of Basic and Biomedical Sciences, University Paris Cité & Inserm UMR_S1124, Paris, France.
Gaelle BruneteauCentre de Recherche en Myologie, UMRS974, Association Institut de Myologie, Sorbonne Université, INSERM, Paris, France.
Delphine SapalyFaculty of Basic and Biomedical Sciences, University Paris Cité & Inserm UMR_S1124, Paris, France.
Sabrina BendrisFaculty of Basic and Biomedical Sciences, University Paris Cité & Inserm UMR_S1124, Paris, France.
Cynthia BezierFaculty of Basic and Biomedical Sciences, University Paris Cité & Inserm UMR_S1124, Paris, France.
Zoé ClercFaculty of Basic and Biomedical Sciences, University Paris Cité & Inserm UMR_S1124, Paris, France.
Elias Abi AkarFaculty of Basic and Biomedical Sciences, University Paris Cité & Inserm UMR_S1124, Paris, France.
Laure WeillFaculty of Basic and Biomedical Sciences, University Paris Cité & Inserm UMR_S1124, Paris, France.
Assaad A EidDepartment of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine and Medical Center, American University of Beirut, Beirut, Lebanon.
Frédéric CharbonnierFaculty of Basic and Biomedical Sciences, University Paris Cité & Inserm UMR_S1124, Paris, France.
Inserm · FRSorbonne Paris Cité · FRAmerican University of Beirut · LBUniversité Paris Cité · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: Spinal muscular atrophy (SMA) is a fatal neurodegenerative disorder, characterized by motor neuron (MN) degeneration and severe muscular atrophy and caused by Survival of Motor Neuron (SMN) depletion. Therapies aimed at increasing SMN in patients have proven their efficiency in alleviating SMA symptoms but not for all patients. Thus, combinational therapies are warranted. Here, we investigated the involvement of NADPH oxidase 4 (NOX4) in SMA-induced spinal MN death and if the modulation of Nox4 activity could be beneficial for SMA patients. Methods: We analysed in the spinal cord of severe type SMA-like mice before and at the disease onset, the level of oxidative stress and Nox4 expression. Then, we tested the effect of Nox4 inhibition by GKT137831/Setanaxib, a drug presently in clinical development, by intrathecal injection on MN survival and motor behaviour. Finally, we tested if GKT137831/Setanaxib could act synergistically with FDA-validated SMN-upregulating treatment (nusinersen). Results: We show that NOX4 is overexpressed in SMA and its inhibition by GKT137831/Setanaxib protected spinal MN from SMA-induced degeneration. These improvements were associated with a significant increase in lifespan and motor behaviour of the mice. At the molecular level, GKT137831 activated the pro-survival AKT/CREB signaling pathway, leading to an increase in SMN expression in SMA MNs. Most importantly, we found that the Conclusion: The pharmacological inhibition of NOX4 by GKT137831/Setanaxib is neuroprotector and could represent a complementary therapeutic strategy to fight against SMA.

Indexed as

GKT137831NADPH oxidase 4neurodegenerative disordersoxidative stressSetanaxibsevere type SMA-like miceSpinal muscular atrophy

Identifiers

PMID37780204
PMCPMC10536974
OpenAlexW4386750723

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

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 Socratic graph.