Growth Differentiation Factor 15 is a potential biomarker of therapeutic response for TK2 deficient myopathy

GDF-15 is a biomarker for mitochondrial diseases. We investigated the application of GDF-15 as biomarker of disease severity and response to deoxynucleoside treatment in patients with thymidine kinase 2 (TK2) deficiency and compared it to FGF-21. GDF-15 and FGF-21 were measured in serum from 24 pati...

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Autores: Domínguez González, Cristina, Badosa, Carmen, Madruga Garrido, Marcos, Martí, Itxaso, Paradas, Carmen, Ortez, Carlos Ignacio, Díaz Manera, Jordi, Berardo, Andrés, Alonso Pérez, Jorge, Trifunov, Selena, Cuadras, Daniel, Kalko, Susana G., Blázquez Bermejo, Cora, Cámara Navarro, Yolanda, Martí, Ramon, Mavillard, Fabiola, Martín, Miguel A., Montoya, Julio, Ruíz Pesini, Eduardo, Villarroya i Terrade, Joan, Montero Sánchez, Raquel, Villarroya i Gombau, Francesc, Artuch Iriberri, Rafael, Hirano, Michio, Nascimento, Andrés, Jiménez Mallebrera, Cecilia
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/176888
Acceso en línea:https://hdl.handle.net/2445/176888
Access Level:acceso abierto
Palabra clave:Marcadors bioquímics
Mitocondris
Biochemical markers
Mitochondria
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spelling Growth Differentiation Factor 15 is a potential biomarker of therapeutic response for TK2 deficient myopathyDomínguez González, CristinaBadosa, CarmenMadruga Garrido, MarcosMartí, ItxasoParadas, CarmenOrtez, Carlos IgnacioDíaz Manera, JordiBerardo, AndrésAlonso Pérez, JorgeTrifunov, SelenaCuadras, DanielKalko, Susana G.Blázquez Bermejo, CoraCámara Navarro, YolandaMartí, RamonMavillard, FabiolaMartín, Miguel A.Montoya, JulioRuíz Pesini, EduardoVillarroya i Terrade, JoanMontero Sánchez, RaquelVillarroya i Gombau, FrancescArtuch Iriberri, RafaelHirano, MichioNascimento, AndrésJiménez Mallebrera, CeciliaMarcadors bioquímicsMitocondrisBiochemical markersMitochondriaGDF-15 is a biomarker for mitochondrial diseases. We investigated the application of GDF-15 as biomarker of disease severity and response to deoxynucleoside treatment in patients with thymidine kinase 2 (TK2) deficiency and compared it to FGF-21. GDF-15 and FGF-21 were measured in serum from 24 patients with TK2 deficiency treated 1-49 months with oral deoxynucleosides. Patients were grouped according to age at treatment and biomarkers were analyzed at baseline and various time points after treatment initiation. GDF-15 was elevated on average 30-fold in children and 6-fold in adults before the start of treatment. There was a significant correlation between basal GDF-15 and severity based on pretreatment distance walked (6MWT) and weight (BMI). During treatment, GDF-15 significantly declined, and the decrease was accompanied by relevant clinical improvements. The decline was greater in the paediatric group, which included the most severe patients and showed the greatest clinical benefit, than in the adult patients. The decline of FGF-21 was less prominent and consistent. GDF-15 is a potential biomarker of severity and of therapeutic response for patients with TK2 deficiency. In addition, we show evidence of clinical benefit of deoxynucleoside treatment, especially when treatment is initiated at an early age.Nature Publishing Group2021202120202021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion13 p.application/pdfhttps://hdl.handle.net/2445/176888Articles publicats en revistes (Bioquímica i Biomedicina Molecular)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1038/s41598-020-66940-8Scientific Reports, 2020, vol. 10, num. 1, p. 10111https://doi.org/10.1038/s41598-020-66940-8cc-by (c) Domínguez González, Cristina et al., 2020http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1768882026-05-29T05:05:01Z
dc.title.none.fl_str_mv Growth Differentiation Factor 15 is a potential biomarker of therapeutic response for TK2 deficient myopathy
title Growth Differentiation Factor 15 is a potential biomarker of therapeutic response for TK2 deficient myopathy
spellingShingle Growth Differentiation Factor 15 is a potential biomarker of therapeutic response for TK2 deficient myopathy
Domínguez González, Cristina
Marcadors bioquímics
Mitocondris
Biochemical markers
Mitochondria
title_short Growth Differentiation Factor 15 is a potential biomarker of therapeutic response for TK2 deficient myopathy
title_full Growth Differentiation Factor 15 is a potential biomarker of therapeutic response for TK2 deficient myopathy
title_fullStr Growth Differentiation Factor 15 is a potential biomarker of therapeutic response for TK2 deficient myopathy
title_full_unstemmed Growth Differentiation Factor 15 is a potential biomarker of therapeutic response for TK2 deficient myopathy
title_sort Growth Differentiation Factor 15 is a potential biomarker of therapeutic response for TK2 deficient myopathy
dc.creator.none.fl_str_mv Domínguez González, Cristina
Badosa, Carmen
Madruga Garrido, Marcos
Martí, Itxaso
Paradas, Carmen
Ortez, Carlos Ignacio
Díaz Manera, Jordi
Berardo, Andrés
Alonso Pérez, Jorge
Trifunov, Selena
Cuadras, Daniel
Kalko, Susana G.
Blázquez Bermejo, Cora
Cámara Navarro, Yolanda
Martí, Ramon
Mavillard, Fabiola
Martín, Miguel A.
Montoya, Julio
Ruíz Pesini, Eduardo
Villarroya i Terrade, Joan
Montero Sánchez, Raquel
Villarroya i Gombau, Francesc
Artuch Iriberri, Rafael
Hirano, Michio
Nascimento, Andrés
Jiménez Mallebrera, Cecilia
author Domínguez González, Cristina
author_facet Domínguez González, Cristina
Badosa, Carmen
Madruga Garrido, Marcos
Martí, Itxaso
Paradas, Carmen
Ortez, Carlos Ignacio
Díaz Manera, Jordi
Berardo, Andrés
Alonso Pérez, Jorge
Trifunov, Selena
Cuadras, Daniel
Kalko, Susana G.
Blázquez Bermejo, Cora
Cámara Navarro, Yolanda
Martí, Ramon
Mavillard, Fabiola
Martín, Miguel A.
Montoya, Julio
Ruíz Pesini, Eduardo
Villarroya i Terrade, Joan
Montero Sánchez, Raquel
Villarroya i Gombau, Francesc
Artuch Iriberri, Rafael
Hirano, Michio
Nascimento, Andrés
Jiménez Mallebrera, Cecilia
author_role author
author2 Badosa, Carmen
Madruga Garrido, Marcos
Martí, Itxaso
Paradas, Carmen
Ortez, Carlos Ignacio
Díaz Manera, Jordi
Berardo, Andrés
Alonso Pérez, Jorge
Trifunov, Selena
Cuadras, Daniel
Kalko, Susana G.
Blázquez Bermejo, Cora
Cámara Navarro, Yolanda
Martí, Ramon
Mavillard, Fabiola
Martín, Miguel A.
Montoya, Julio
Ruíz Pesini, Eduardo
Villarroya i Terrade, Joan
Montero Sánchez, Raquel
Villarroya i Gombau, Francesc
Artuch Iriberri, Rafael
Hirano, Michio
Nascimento, Andrés
Jiménez Mallebrera, Cecilia
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Marcadors bioquímics
Mitocondris
Biochemical markers
Mitochondria
topic Marcadors bioquímics
Mitocondris
Biochemical markers
Mitochondria
description GDF-15 is a biomarker for mitochondrial diseases. We investigated the application of GDF-15 as biomarker of disease severity and response to deoxynucleoside treatment in patients with thymidine kinase 2 (TK2) deficiency and compared it to FGF-21. GDF-15 and FGF-21 were measured in serum from 24 patients with TK2 deficiency treated 1-49 months with oral deoxynucleosides. Patients were grouped according to age at treatment and biomarkers were analyzed at baseline and various time points after treatment initiation. GDF-15 was elevated on average 30-fold in children and 6-fold in adults before the start of treatment. There was a significant correlation between basal GDF-15 and severity based on pretreatment distance walked (6MWT) and weight (BMI). During treatment, GDF-15 significantly declined, and the decrease was accompanied by relevant clinical improvements. The decline was greater in the paediatric group, which included the most severe patients and showed the greatest clinical benefit, than in the adult patients. The decline of FGF-21 was less prominent and consistent. GDF-15 is a potential biomarker of severity and of therapeutic response for patients with TK2 deficiency. In addition, we show evidence of clinical benefit of deoxynucleoside treatment, especially when treatment is initiated at an early age.
publishDate 2020
dc.date.none.fl_str_mv 2020
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/176888
url https://hdl.handle.net/2445/176888
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1038/s41598-020-66940-8
Scientific Reports, 2020, vol. 10, num. 1, p. 10111
https://doi.org/10.1038/s41598-020-66940-8
dc.rights.none.fl_str_mv cc-by (c) Domínguez González, Cristina et al., 2020
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Domínguez González, Cristina et al., 2020
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 13 p.
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
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repository.mail.fl_str_mv
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