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Analysis of institutional authors

Mateu-Bosch, AAuthorSegur-Bailach, EAuthorGarcia-Villoria, JAuthorGea-Sorlí, SAuthorRuiz, IAuthorDel Rey, JAuthorCamps, JAuthorGuitart-Mampel, MAuthorGarrabou, GAuthorTort, FAuthorRibes, AAuthorFillat, CCorresponding Author

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January 3, 2024
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Modeling Glutaric Aciduria Type I in human neuroblastoma cells recapitulates neuronal damage that can be rescued by gene replacement

Publicated to: Gene Therapy. 31 (1-2): 12-18 - 2024-01-01 31(1-2), DOI: 10.1038/s41434-023-00428-8

Authors:

Mateu-Bosch, A; Segur-Bailach, E; García-Villoria, J; Gea-Sorlí, S; Ruiz, I; del Rey, J; Camps, J; Guitart-Mampel, M; Garrabou, G; Tort, F; Ribes, A; Fillat, C
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Affiliations

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain. - Author
Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain. - Author
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Barcelona, Spain - Author
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Barcelona, Spain - Author
Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), Barcelona, Spain. - Author
Hosp Clin Barcelona, Biochemial & Mol Genet Dept, Sect Inborn Errors Metab IBC, Barcelona, Spain - Author
Inherited Metab Dis & Muscle DisordersResearch Grp, Barcelona, Spain - Author
Inst Invest Biomed August Pi i Sunyer IDIBAPS, Barcelona, Spain - Author
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. - Author
Unitat de Biologia Cel·lular i Genètica Mèdica, Departament de Biologia Cel·lular, Fisiologia i Immunologia, Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, 08193, Spain. - Author
Univ Autonoma Barcelona, Fac Med, Dept Biol Cellular Fisiol & Immunol, Unitat Biol Cellular & Genet Med, Bellaterra 08193, Spain - Author
Univ Barcelona UB, Fac Med & Ciencies Salut, Barcelona, Spain - Author
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Abstract

Glutaric Aciduria type I (GA1) is a rare neurometabolic disorder caused by mutations in the GDCH gene encoding for glutaryl-CoA dehydrogenase (GCDH) in the catabolic pathway of lysine, hydroxylysine and tryptophan. GCDH deficiency leads to increased concentrations of glutaric acid (GA) and 3-hydroxyglutaric acid (3-OHGA) in body fluids and tissues. These metabolites are the main triggers of brain damage. Mechanistic studies supporting neurotoxicity in mouse models have been conducted. However, the different vulnerability to some stressors between mouse and human brain cells reveals the need to have a reliable human neuronal model to study GA1 pathogenesis. In the present work we generated a GCDH knockout (KO) in the human neuroblastoma cell line SH-SY5Y by CRISPR/Cas9 technology. SH-SY5Y-GCDH KO cells accumulate GA, 3-OHGA, and glutarylcarnitine when exposed to lysine overload. GA or lysine treatment triggered neuronal damage in GCDH deficient cells. SH-SY5Y-GCDH KO cells also displayed features of GA1 pathogenesis such as increased oxidative stress vulnerability. Restoration of the GCDH activity by gene replacement rescued neuronal alterations. Thus, our findings provide a human neuronal cellular model of GA1 to study this disease and show the potential of gene therapy to rescue GCDH deficiency.
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Keywords

3 hydroxyglutaric acid3 phosphogycerate kinaseAminoAmino acid metabolism, inborn errorsAnimalAnimalsArticleAstrocytesBrain diseasesBrain diseases, metabolicCarnitineCell damageControlled studyCrispr-cas9 systemDeath implicationsDehydrogenase deficient miceDisorders of amino acid and protein metabolismEnzyme activityEnzyme deficiencyGene insertionGene knockoutGene replacement therapyGene therapyGenetic therapyGeneticsGlutaric acidGlutaric acidemia iGlutaric aciduria type 1Glutaryl coenzyme a dehydrogenaseGlutaryl-coa dehydrogenaseGlutarylcarnitineHumanHuman cellHumansKnockout mouseLysineMalalties cerebralsMetabolic encephalopathyMetabolismMiceMice, knockoutMouseMouse modelNerve injuryNeuroblastomaNeuroblastoma cellNeurodegenerationOxidative stressPathogenesisPhenotypePhosphotransferasePromoter regionProteïnesProteinsSh-sy5y cell lineSusceptibilityTeràpia genèticaUnclassified drug

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Gene Therapy due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2024 there are still no calculated indicators, but in 2023, it was in position 31/191, thus managing to position itself as a Q1 (Primer Cuartil), in the category Genetics & Heredity.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2025-12-26:

  • WoS: 3
  • Scopus: 3
  • Europe PMC: 1
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Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-12-26:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 8.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 8 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 1.
  • The number of mentions on the social network X (formerly Twitter): 1 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

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Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Mateu Bosch, Anna) and Last Author (Fillat Fonts, Cristina).

the author responsible for correspondence tasks has been Fillat Fonts, Cristina.

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Awards linked to the item

AM-B is recipient of a PIF-Salut predoctoral contract from Generalitat de Catalunya,Spain. MG-M is recipient of a Sara Borrell contract CD21/00019 from Instituto de Salud Carlos III (ISCIII). This work was supported by grants to CF from the CIVP19A5949-Fundacion Ramon Areces, Merck Sharp Dohme Espana S.A, ACCI-CIBERER (ER21P2AC737) and PID2020-119692RB-C22 Spanish Ministerio de Ciencia e Innovacion, with partial support from the Generalitat de Catalunya SGR2021/01169 and SGR2021/01423. It also acknowledges the support of CHARLIE Consortium, a project supported by ISCIII under the frame of E-Rare-3, the ERA-Net for Research on Rare Diseases, EJPRD grant nr: 825575. CIBERER is an initiative of the ISCIII. We also acknowledge the support of CERCA Program/Generalitat de Catalunya. This work was developed at the Centro Esther Koplowitz, Barcelona, Spain.
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