Evidence map›Paper›PMID 41411050›Full record

ArticleJCI insight2026

Splice modulation of COL4A5 reinstates collagen IV assembly in an organoid model of Alport syndrome.

Hassan Saei, Bruno Estebe, Nicolas Goudin, Mahsa Esmailpour, Julie Haure, Olivier Gribouval, Christelle Arrondel, Vincent Moriniere, Pinyuan Tian, Rachel Lennon and 3 more

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In one paragraph

Article in JCI insight, 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

13 authors.

Hassan SaeiLaboratory of Hereditary Kidney Diseases, INSERM UMR 1163, Imagine Institute, Université Paris Cité, Paris, France.
Bruno EstebeLaboratory of Hereditary Kidney Diseases, INSERM UMR 1163, Imagine Institute, Université Paris Cité, Paris, France.
Nicolas GoudinNecker Bioimage Analysis Core Facility of the Structure Fédérative de Recherche Necker, INSERM US24/CNRS UAR 3633, Paris, France.
Mahsa EsmailpourLaboratory of Hereditary Kidney Diseases, INSERM UMR 1163, Imagine Institute, Université Paris Cité, Paris, France.
Julie HaureLaboratory of Hereditary Kidney Diseases, INSERM UMR 1163, Imagine Institute, Université Paris Cité, Paris, France.
Olivier GribouvalLaboratory of Hereditary Kidney Diseases, INSERM UMR 1163, Imagine Institute, Université Paris Cité, Paris, France.
Christelle ArrondelLaboratory of Hereditary Kidney Diseases, INSERM UMR 1163, Imagine Institute, Université Paris Cité, Paris, France.
Vincent MoriniereDepartment of Genomic Medicine for Rare Diseases, Necker-Enfants Malades Hospital, Assistance publique, Hôpitaux de Paris (AP-HP), Paris, France.
Pinyuan TianWellcome Trust Centre for Cell-Matrix Research, University of Manchester, Manchester, United Kingdom.
Rachel LennonWellcome Trust Centre for Cell-Matrix Research, University of Manchester, Manchester, United Kingdom.
Corinne AntignacLaboratory of Hereditary Kidney Diseases, INSERM UMR 1163, Imagine Institute, Université Paris Cité, Paris, France.
Geraldine MolletLaboratory of Hereditary Kidney Diseases, INSERM UMR 1163, Imagine Institute, Université Paris Cité, Paris, France.
Guillaume DorvalLaboratory of Hereditary Kidney Diseases, INSERM UMR 1163, Imagine Institute, Université Paris Cité, Paris, France.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Kidney organoids are an emerging tool for disease modeling, especially genetic diseases. Among these diseases, X-linked Alport syndrome (XLAS) is a hematuric nephropathy affecting the glomerular basement membrane (GBM) secondary to pathogenic variations in the COL4A5 gene encoding the α5 subunit of type IV collagen [α5(IV)]. In patients carrying pathogenic variations affecting splicing, the use of antisense oligonucleotides (ASOs) offers immense therapeutic hope. In this study, we develop a framework combining the use of patient-derived cells and kidney organoids to provide evidence of the therapeutic efficacy of ASOs in XLAS patients. Using multiomics analysis, we describe the development of GBM in WT and mutated human kidney organoids. We show that GBM maturation is a dynamic process, which requires long organoid culture. Then, using semi-automated quantification of α5(IV) at basement membranes in organoids carrying the splicing variants identified in patients, we demonstrate the efficacy of ASO treatment for α5(IV) restoration. These data contribute to our understanding of the development of GBM in kidney organoids and pave the way for a therapeutic screening platform for patients.

Indexed as

Collagen Type IVNephritis, HereditaryOrganoidsGlomerular Basement MembraneHumansKidneyMutationOligonucleotides, AntisenseRNA SplicingCOL4A5 protein, humanCollagen Type IVOligonucleotides, AntisenseChronic kidney diseaseCollagensGeneticsNephrologyTherapeutics

Identifiers

PMID41411050
PMCPMC12892906

What Socratic holds

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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.