Myostatin and follistatin as monitoring and prognostic biomarkers in dysferlinopathy
Por:
Moore U., Fernández-Simón E., Schiava M., Cox D., Gordish-Dressman H., James M.K., Mayhew A., Wilson I., Guglieri M., Rufibach L., Blamire A., Carlier P.G., Mori-Yoshimura M., Day J.W., Jones K.J., Bharucha-Goebel D.X., Salort-Campana E., Pestronk A., Walter M.C., Paradas C., Stojkovic T., Bravver E., Pegoraro E., Mendell J.R., Bushby K., Diaz-Manera J., Straub V.
Publicada:
1 ene 2023
Ahead of Print:
1 ene 2023
Resumen:
Myostatin is a myokine which acts upon skeletal muscle to inhibit growth and regeneration. Myostatin is endogenously antagonised by follistatin. This study assessed serum myostatin and follistatin concentrations as monitoring or prognostic biomarkers in dysferlinopathy, an autosomal recessively inherited muscular dystrophy. Myostatin was quantified twice with a three-year interval in 76 patients with dysferlinopathy and 38 controls. Follistatin was quantified in 62 of these patients at the same timepoints, and in 31 controls. Correlations with motor function, muscle fat fraction and contractile cross-sectional area were performed. A regression model was used to account for confounding variables. Baseline myostatin, but not follistatin, correlated with baseline function and MRI measures. However, in individual patients, three-year change in myostatin did not correlate with functional or MRI changes. Linear modelling demonstrated that function, serum creatine kinase and C-reactive protein, but not age, were independently related to myostatin concentration. Baseline myostatin concentration predicted loss of ambulation but not rate of change of functional or MRI measures, even when relative inhibition with follistatin was considered. With adjustment for extra-muscular causes of variation, myostatin could form a surrogate measure of functional ability or muscle mass, however myostatin inhibition does not form a promising treatment target in dysferlinopathy. Copyright © 2023. Published by Elsevier B.V.
Filiaciones:
Moore U.:
John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
Fernández-Simón E.:
John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
Schiava M.:
John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
Cox D.:
John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
Gordish-Dressman H.:
Center for Translational Science, Division of Biostatistics and Study Methodology, Children's National Health System, Washington, DC, USA
James M.K.:
John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
Mayhew A.:
John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
Wilson I.:
Magnetic Resonance Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom
Guglieri M.:
John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
Rufibach L.:
Jain Foundation, Seattle, WA, United States
Blamire A.:
Magnetic Resonance Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom
Carlier P.G.:
University Paris-Saclay, CEA, Spain
Mori-Yoshimura M.:
Department of Neurology, National Center Hospital, National Center of Neurology and PsychiatryTokyo, Japan
Day J.W.:
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, United States
Jones K.J.:
Children's Hospital at Westmead and The University of Sydney, NSW, Sydney, Australia
Bharucha-Goebel D.X.:
Department of Neurology, Children's National Health System, Washington, DC, USA
Salort-Campana E.:
Service des maladies neuromusculaire et de la SLA, Hôpital de La Timone, Marseille, France
Pestronk A.:
Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
Walter M.C.:
Friedrich-Baur-Institute, Department of Neurology, LudwigMaximilians-University of Munich, Munich, Germany
Paradas C.:
Neuromuscular Unit, Department of Neurology, Hospital U. Virgen del Rocío/Instituto de Biomedicina de Sevilla, Sevilla, Spain
Stojkovic T.:
Centre de reference des maladies neuromusculaires, Institut de Myologie, AP-HP, Sorbonne Université, Hôpital Pitié-Salpêtrière, Paris, France
Bravver E.:
Neuroscience Institute, Carolinas Neuromuscular/ALS-MDA Center, Carolinas HealthCare System, Charlotte, NC, USA
Pegoraro E.:
Department of Neuroscience, University of Padova, Padua, Italy
Mendell J.R.:
Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, United States
Bushby K.:
John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
Diaz-Manera J.:
The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
Straub V.:
John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
hybrid, All Open Access; Hybrid Gold
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