Identification of serum microRNAs as potential biomarkers in Pompe disease

Ana Carrasco-Rozas, Esther Fernández-Simón, Maria Cinta Lleixà, Izaskun Belmonte, Irene Pedrosa-Hernandez, Elena Montiel-Morillo, Claudia Nuñez-Peralta, Jaume Llauger Rossello, Sonia Segovia, Noemí De Luna, Xavier Suarez-Calvet, Isabel Illa, Pompe Spanish Study group, Jordi Díaz-Manera, Eduard Gallardo, Miguel Angel Barba-Romero, Joseba Barcena, María Rosario Carzorla, Carlota Creus, Jaume Coll-Cantí, Manuel Díaz, Cristina Domínguez, Roberto Fernández Torrón, María José García Antelo, Josep María Grau, María Teresa Gómez Caravaca, Juan Carlos León Hernández, Adolfo López de Munáin, Francisco Antonio Martínez-García, Yolanda Morgado, Antonio Moreno, Miguel Angel Muñoz-Blanco, Andres Nascimento, Carmen Paradas, José Luis Parajuá Pozo, Luis Querol, Arturo Robledo-Strauss, Ricard Rojas García, Íñigo Rojas-Marcos, Jose Antonio Salazar, Mercedes Usón, Ana Carrasco-Rozas, Esther Fernández-Simón, Maria Cinta Lleixà, Izaskun Belmonte, Irene Pedrosa-Hernandez, Elena Montiel-Morillo, Claudia Nuñez-Peralta, Jaume Llauger Rossello, Sonia Segovia, Noemí De Luna, Xavier Suarez-Calvet, Isabel Illa, Pompe Spanish Study group, Jordi Díaz-Manera, Eduard Gallardo, Miguel Angel Barba-Romero, Joseba Barcena, María Rosario Carzorla, Carlota Creus, Jaume Coll-Cantí, Manuel Díaz, Cristina Domínguez, Roberto Fernández Torrón, María José García Antelo, Josep María Grau, María Teresa Gómez Caravaca, Juan Carlos León Hernández, Adolfo López de Munáin, Francisco Antonio Martínez-García, Yolanda Morgado, Antonio Moreno, Miguel Angel Muñoz-Blanco, Andres Nascimento, Carmen Paradas, José Luis Parajuá Pozo, Luis Querol, Arturo Robledo-Strauss, Ricard Rojas García, Íñigo Rojas-Marcos, Jose Antonio Salazar, Mercedes Usón

Abstract

Objective: To analyze the microRNA profile in serum of patients with Adult Onset Pompe disease (AOPD).

Methods: We analyzed the expression of 185 microRNAs in serum of 15 AOPD patients and five controls using microRNA PCR Panels. The expression levels of microRNAs that were deregulated were further studied in 35 AOPD patients and 10 controls using Real-Time PCR. Additionally, the skeletal muscle expression of microRNAs which showed significant increase levels in serum samples was also studied. Correlations between microRNA serum levels and muscle function test, spirometry, and quantitative muscle MRI were performed (these data correspond to the study NCT01914536 at ClinicalTrials.gov).

Results: We identified 14 microRNAs that showed different expression levels in serum samples of AOPD patients compared to controls. We validated these results in a larger cohort of patients and we found increased levels of three microRNAs, the so called dystromirs: miR-1-3p, miR-133a-3p, and miR-206. These microRNAs are involved in muscle regeneration and the expression of these was increased in patients' muscle biopsies. Significant correlations between microRNA levels and muscle function test were found.

Interpretation: Serum expression levels of dystromirs may represent additional biomarkers for the follow-up of AOPD patients.

Conflict of interest statement

This study (GZ‐2015‐11342) has been performed with funding from SANOFI/Genzyme.

© 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.

Figures

Figure 1
Figure 1
Normalized relative expression levels of validated serum miRNAs in Pompe patients. Data are presented as mean ± SD. Mann–Whitney U test *P < 0.05, **P < 0.01 and ***P < 0.001.
Figure 2
Figure 2
Normalized relative expression levels of serum miRNAs in Pompe patients. Data are presented as mean ± SD. Mann–Whitney U test.
Figure 3
Figure 3
Dystromir expression changes in Pompe patients in response to the treatment. Data are presented as fold change values in post‐ERT patients regarding their pre‐ERT samples.
Figure 4
Figure 4
Normalized relative expression levels of muscle miRNAs in Pompe patients. Data are presented as mean ± SD. Mann–Whitney U test *P < 0.05.

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