Platelet Derived Growth Factor-AA Correlates With Muscle Function Tests and Quantitative Muscle Magnetic Resonance in Dystrophinopathies
Por:
Alonso-Jiménez A, Fernández-Simón E, Natera-de Benito D, Ortez-Gonzalez CI, García C, Montiel E, Belmonte I, Pedrosa I, Segovia S, Piñol-Jurado P, Carrasco-Rozas A, Suárez-Calvet X, Jimenez-Mallebrera C, Nascimento-Osorio A, Llauger J, Nuñez-Peralta C, Montesinos P, Alonso-Pérez J, Gallardo E, Illa I and Díaz-Manera J
Publicada:
11 jun 2021
Ahead of Print:
11 jun 2021
Resumen:
Introduction: Duchenne (DMD) and Becker (BMD) muscular dystrophy are X-linked muscular disorders produced by mutations in the DMD gene which encodes the protein dystrophin. Both diseases are characterized by progressive involvement of skeletal, cardiac, and respiratory muscles. As new treatment strategies become available, reliable biomarkers and outcome measures that can monitor disease progression are needed for clinical trials. Methods: We collected clinical and functional data and blood samples from 19 DMD patients, 13 BMD patients, and 66 healthy controls (8 pediatric and 58 adult controls), and blood samples from 15 patients with dysferlinopathy (DYSF) and studied the serum concentration of 4 growth factors involved in the process of muscle fibrosis. We correlated the serum concentration of these growth factors with several muscle function tests, spirometry results and fat fraction identified by quantitative Dixon muscle MRI. Results: We found significant differences in the serum concentration of Platelet Derived Growth Factor-AA (PDGF-AA) between DMD patients and pediatric controls, in Connective Tissue Growth Factor (CTGF) between BMD patients and adult controls, and in and Transforming Growth Factor- beta 1 (TGF-beta 1) between BMD and DYSF patients. PDGF-AA showed a good correlation with several muscle function tests for both DMD and BMD patients and with thigh fat fraction in BMD patients. Moreover, PDGF-AA levels were increased in muscle biopsies of patients with DMD and BMD as was demonstrated by immunohistochemistry and Real-Time PCR studies. Conclusion: Our study suggests that PDGF-AA should be further investigated in a larger cohort of DMD and BMD patients because it might be a good biomarker candidate to monitor the progression of these diseases.
Filiaciones:
Alonso-Jiménez A:
Neuromuscular Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Departament de Medicina. Universitat Autònoma de Barcelona, Barcelona, Spain
Neurology Department, Neuromuscular Reference Center, University Hospital of Antwerp, Antwerp, Belgium
Fernández-Simón E:
Neuromuscular Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Departament de Medicina. Universitat Autònoma de Barcelona, Barcelona, Spain
Biomedical Network Research Centre on Rare Diseases (CIBERER), Barcelona, Spain
John Walton Muscular Dystrophy Research Centre, International Centre for Life, Newcastle University, Newcastle upon Tyne, United Kingdom
Natera-de Benito D:
Neuromuscular Unit, Neuropediatrics Department, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, Barcelona, Spain
Ortez-Gonzalez CI:
Neuromuscular Unit, Neuropediatrics Department, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, Barcelona, Spain
García C:
Rehabilitation and Physiotherapy Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
Montiel E:
Rehabilitation and Physiotherapy Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
Belmonte I:
Rehabilitation and Physiotherapy Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
Pedrosa I:
Rehabilitation and Physiotherapy Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
Segovia S:
Neuromuscular Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Departament de Medicina. Universitat Autònoma de Barcelona, Barcelona, Spain
Biomedical Network Research Centre on Rare Diseases (CIBERER), Barcelona, Spain
Piñol-Jurado P:
Neuromuscular Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Departament de Medicina. Universitat Autònoma de Barcelona, Barcelona, Spain
Biomedical Network Research Centre on Rare Diseases (CIBERER), Barcelona, Spain
John Walton Muscular Dystrophy Research Centre, International Centre for Life, Newcastle University, Newcastle upon Tyne, United Kingdom
Carrasco-Rozas A:
Neuromuscular Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Departament de Medicina. Universitat Autònoma de Barcelona, Barcelona, Spain
Biomedical Network Research Centre on Rare Diseases (CIBERER), Barcelona, Spain
Suárez-Calvet X:
Neuromuscular Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Departament de Medicina. Universitat Autònoma de Barcelona, Barcelona, Spain
Biomedical Network Research Centre on Rare Diseases (CIBERER), Barcelona, Spain
Jimenez-Mallebrera C:
Biomedical Network Research Centre on Rare Diseases (CIBERER), Barcelona, Spain
Neuromuscular Unit, Neuropediatrics Department, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, Barcelona, Spain
Departamento de Genética, Microbiología y Estadística, Universidad de Barcelona, Barcelona, Spain
Nascimento-Osorio A:
Biomedical Network Research Centre on Rare Diseases (CIBERER), Barcelona, Spain
Neuromuscular Unit, Neuropediatrics Department, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, Barcelona, Spain
Llauger J:
Radiology Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
Nuñez-Peralta C:
Radiology Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
Montesinos P:
Philips Healthcare Iberia, Madrid, Spain
Alonso-Pérez J:
Neuromuscular Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Departament de Medicina. Universitat Autònoma de Barcelona, Barcelona, Spain
Biomedical Network Research Centre on Rare Diseases (CIBERER), Barcelona, Spain
Gallardo E:
Neuromuscular Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Departament de Medicina. Universitat Autònoma de Barcelona, Barcelona, Spain
Biomedical Network Research Centre on Rare Diseases (CIBERER), Barcelona, Spain
Illa I:
Neuromuscular Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Departament de Medicina. Universitat Autònoma de Barcelona, Barcelona, Spain
Biomedical Network Research Centre on Rare Diseases (CIBERER), Barcelona, Spain
Díaz-Manera J:
Neuromuscular Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Departament de Medicina. Universitat Autònoma de Barcelona, Barcelona, Spain
Biomedical Network Research Centre on Rare Diseases (CIBERER), Barcelona, Spain
John Walton Muscular Dystrophy Research Centre, International Centre for Life, Newcastle University, Newcastle upon Tyne, United Kingdom
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