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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 principales: Dominguez-Gonzalez, Cristina, Badosa, Carmen, Madruga-Garrido, Marcos, Martí, Itxaso, Paradas, Carmen, Ortez, Carlos, Diaz-Manera, Jordi, Berardo, Andres, Alonso-Pérez, Jorge, Trifunov, Selena, Cuadras, Daniel, Kalko, Susana G., Blázquez-Bermejo, Cora, Cámara, Yolanda, Martí, Ramon, Mavillard, Fabiola, Martin, Miguel A., Montoya, Julio, Ruiz-Pesini, Eduardo, Villarroya, Joan, Montero, Raquel, Villarroya, Francesc, Artuch, Rafael, Hirano, Michio, Nascimento, Andrés, Jimenez-Mallebrera, Cecilia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308386/
https://www.ncbi.nlm.nih.gov/pubmed/32572108
http://dx.doi.org/10.1038/s41598-020-66940-8
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author Dominguez-Gonzalez, Cristina
Badosa, Carmen
Madruga-Garrido, Marcos
Martí, Itxaso
Paradas, Carmen
Ortez, Carlos
Diaz-Manera, Jordi
Berardo, Andres
Alonso-Pérez, Jorge
Trifunov, Selena
Cuadras, Daniel
Kalko, Susana G.
Blázquez-Bermejo, Cora
Cámara, Yolanda
Martí, Ramon
Mavillard, Fabiola
Martin, Miguel A.
Montoya, Julio
Ruiz-Pesini, Eduardo
Villarroya, Joan
Montero, Raquel
Villarroya, Francesc
Artuch, Rafael
Hirano, Michio
Nascimento, Andrés
Jimenez-Mallebrera, Cecilia
author_facet Dominguez-Gonzalez, Cristina
Badosa, Carmen
Madruga-Garrido, Marcos
Martí, Itxaso
Paradas, Carmen
Ortez, Carlos
Diaz-Manera, Jordi
Berardo, Andres
Alonso-Pérez, Jorge
Trifunov, Selena
Cuadras, Daniel
Kalko, Susana G.
Blázquez-Bermejo, Cora
Cámara, Yolanda
Martí, Ramon
Mavillard, Fabiola
Martin, Miguel A.
Montoya, Julio
Ruiz-Pesini, Eduardo
Villarroya, Joan
Montero, Raquel
Villarroya, Francesc
Artuch, Rafael
Hirano, Michio
Nascimento, Andrés
Jimenez-Mallebrera, Cecilia
author_sort Dominguez-Gonzalez, Cristina
collection PubMed
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.
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spelling pubmed-73083862020-06-23 Growth Differentiation Factor 15 is a potential biomarker of therapeutic response for TK2 deficient myopathy Dominguez-Gonzalez, Cristina Badosa, Carmen Madruga-Garrido, Marcos Martí, Itxaso Paradas, Carmen Ortez, Carlos Diaz-Manera, Jordi Berardo, Andres Alonso-Pérez, Jorge Trifunov, Selena Cuadras, Daniel Kalko, Susana G. Blázquez-Bermejo, Cora Cámara, Yolanda Martí, Ramon Mavillard, Fabiola Martin, Miguel A. Montoya, Julio Ruiz-Pesini, Eduardo Villarroya, Joan Montero, Raquel Villarroya, Francesc Artuch, Rafael Hirano, Michio Nascimento, Andrés Jimenez-Mallebrera, Cecilia Sci Rep Article 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. Nature Publishing Group UK 2020-06-22 /pmc/articles/PMC7308386/ /pubmed/32572108 http://dx.doi.org/10.1038/s41598-020-66940-8 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Dominguez-Gonzalez, Cristina
Badosa, Carmen
Madruga-Garrido, Marcos
Martí, Itxaso
Paradas, Carmen
Ortez, Carlos
Diaz-Manera, Jordi
Berardo, Andres
Alonso-Pérez, Jorge
Trifunov, Selena
Cuadras, Daniel
Kalko, Susana G.
Blázquez-Bermejo, Cora
Cámara, Yolanda
Martí, Ramon
Mavillard, Fabiola
Martin, Miguel A.
Montoya, Julio
Ruiz-Pesini, Eduardo
Villarroya, Joan
Montero, Raquel
Villarroya, Francesc
Artuch, Rafael
Hirano, Michio
Nascimento, Andrés
Jimenez-Mallebrera, Cecilia
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
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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308386/
https://www.ncbi.nlm.nih.gov/pubmed/32572108
http://dx.doi.org/10.1038/s41598-020-66940-8
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