Myostatin and follistatin as monitoring and prognostic biomarkers in dysferlinopathy

Ursula Moore, The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Esther Fernández-Simón, The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Marianela Schiava, The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Dan Cox, The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Heather Gordish-Dressman, Center for Translational Science, Division of Biostatistics and Study Methodology, Children's National Health System, Washington, DC, USA; Pediatrics, Epidemiology and Biostatistics, George Washington University, Washington, DC, USA.
Meredith K. James, The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Anna Mayhew, The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Ian Wilson, Magnetic Resonance Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
Michela Guglieri, The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Laura Rufibach, Jain Foundation, Seattle, WA, USA.
Andrew Blamire, Magnetic Resonance Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
Pierre G. Carlier, University Paris-Saclay, CEA, DRF SHF, Orsay France.
Madoka Mori-Yoshimura, Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.
John W. Day, Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Kristi J. Jones, The Children's Hospital at Westmead and The University of Sydney, Sydney, NSW, Australia.
Diana X. Bharucha-Goebel, Department of Neurology, Children's National Health System, Washington, DC, USA; National Institutes of Health (NINDS), Bethesda, MD, USA.
Emmanuelle Salort-Campana, Service des maladies neuromusculaire et de la SLA, Hôpital de La Timone, Marseille, France.
Alan Pestronk, Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
Maggie C. Walter, Friedrich-Baur-Institute, Department of Neurology, LudwigMaximilians-University of Munich, Munich, Germany.
Carmen Paradas, Neuromuscular Unit, Department of Neurology, Hospital U. Virgen del Rocío/Instituto de Biomedicina de Sevilla, Sevilla, Spain.
Tanya Stojkovic, Centre de reference des maladies neuromusculaires, Institut de Myologie, AP-HP, Sorbonne Université, Hôpital Pitié-Salpêtrière, Paris, France.
Elena Bravver, Neuroscience Institute, Carolinas Neuromuscular/ALS-MDA Center, Carolinas HealthCare System, Charlotte, NC, USA.
Elena Pegoraro, Department of Neuroscience, University of Padova, Padua, Italy.
Jerry R. Mendell, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
Kate Bushby, The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Jordi Diaz-Manera, The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; Neuromuscular Disorders Unit, Neurology Department, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain; Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER), Madrid, Spain.
Volker Straub, The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK. Electronic address: volker.straub@newcastle.ac.uk.

Document Type

Journal Article

Publication Date

1-6-2023

Journal

Neuromuscular disorders : NMD

Volume

33

Issue

2

DOI

10.1016/j.nmd.2023.01.001

Keywords

Dysferlinopathy; Follistatin; Limb girdle muscular dystrophy R2; Miyoshi myopathy; Muscular dystrophy; Myostatin

Abstract

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.

Department

Genomics and Precision Medicine

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