title: Reduced serum myostatin concentrations associated with genetic muscle disease progression.
abstract: Myostatin is a highly conserved protein secreted primarily from skeletal muscle that can potently suppress muscle growth. This ability to regulate skeletal muscle mass has sparked intense interest in the development of anti-myostatin therapies for a wide array of muscle disorders including sarcopenia, cachexia and genetic neuromuscular diseases. While a number of studies have examined the circulating myostatin concentrations in healthy and sarcopenic populations, very little data are available from inherited muscle disease patients. Here, we have measured the myostatin concentration in serum from seven genetic neuromuscular disorder patient populations using immunoaffinity LC-MS/MS. Average serum concentrations of myostatin in all seven muscle disease patient groups were significantly less than those measured in healthy controls. Furthermore, circulating myostatin concentrations correlated with clinical measures of disease progression for five of the muscle disease patient populations. These findings greatly expand the understanding of myostatin in neuromuscular disease and suggest its potential utility as a biomarker of disease progression.
authors.affiliation: Worldwide Research and Development, Pfizer Inc., Eastern Point Road, Groton, CT, 06340, USA. peter.m.burch2@gmail.com.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Burch
authors.affiliation: John Walton Muscular Dystrophy Research Centre, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Oksana
authors.initials: O
authors.lastname: Pogoryelova
authors.affiliation: Worldwide Research and Development, Pfizer Inc., 1 Burtt Rd, Andover, MA, USA.
authors.forename: Joe
authors.initials: J
authors.lastname: Palandra
authors.affiliation: Worldwide Research and Development, Pfizer Inc., Eastern Point Road, Groton, CT, 06340, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Goldstein
authors.affiliation: Worldwide Research and Development, Pfizer Inc., 610 Main St., Cambridge, MA, USA.
authors.forename: Donald
authors.initials: D
authors.lastname: Bennett
authors.affiliation: Worldwide Research and Development, Pfizer Inc., 610 Main St., Cambridge, MA, USA.
authors.forename: Lori
authors.initials: L
authors.lastname: Fitz
authors.affiliation: John Walton Muscular Dystrophy Research Centre, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Michela
authors.initials: M
authors.lastname: Guglieri
authors.affiliation: John Walton Muscular Dystrophy Research Centre, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Chiara Marini
authors.initials: CM
authors.lastname: Bettolo
authors.affiliation: John Walton Muscular Dystrophy Research Centre, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Volker
authors.initials: V
authors.lastname: Straub
authors.affiliation: John Walton Muscular Dystrophy Research Centre, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Teresinha
authors.initials: T
authors.lastname: Evangelista
authors.affiliation: Worldwide Research and Development, Pfizer Inc., 1 Burtt Rd, Andover, MA, USA.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Neubert
authors.affiliation: John Walton Muscular Dystrophy Research Centre, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Hanns
authors.initials: H
authors.lastname: Lochmüller
authors.affiliation: Worldwide Research and Development, Pfizer Inc., 610 Main St., Cambridge, MA, USA.|Solid Biosciences, 161 First St., Cambridge, MA, 02142, USA.
authors.forename: Carl
authors.initials: C
authors.lastname: Morris
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001774:Blood Chemical Analysis; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D055435:Myostatin / Q000097:blood*; D009468:Neuromuscular Diseases / Q000097:blood* / Q000235:genetics; D055815:Young Adult
chemical_list: D015415:Biomarkers; C525911:MSTN protein, human; D055435:Myostatin
keywords: Biomarker; Mass spectrometry; Myostatin; Neuromuscular disease