title: Long-term enhancement of skeletal muscle mass and strength by single gene administration of myostatin inhibitors.
abstract: Increasing the size and strength of muscles represents a promising therapeutic strategy for musculoskeletal disorders, and interest has focused on myostatin, a negative regulator of muscle growth. Various myostatin inhibitor approaches have been identified and tested in models of muscle disease with varying efficacies, depending on the age at which myostatin inhibition occurs. Here, we describe a one-time gene administration of myostatin-inhibitor-proteins to enhance muscle mass and strength in normal and dystrophic mouse models for >2 years, even when delivered in aged animals. These results demonstrate a promising therapeutic strategy that warrants consideration for clinical trials in human muscle diseases.
authors.affiliation: The Research Institute, Nationwide Children's Hospital, Columbus, OH 43205, USA.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Haidet
authors.forename: Liza
authors.initials: L
authors.lastname: Rizo
authors.forename: Chalonda
authors.initials: C
authors.lastname: Handy
authors.forename: Priya
authors.initials: P
authors.lastname: Umapathi
authors.forename: Amy
authors.initials: A
authors.lastname: Eagle
authors.forename: Chris
authors.initials: C
authors.lastname: Shilling
authors.forename: Daniel
authors.initials: D
authors.lastname: Boue
authors.forename: Paul T
authors.initials: PT
authors.lastname: Martin
authors.forename: Zarife
authors.initials: Z
authors.lastname: Sahenk
authors.forename: Jerry R
authors.initials: JR
authors.lastname: Mendell
authors.forename: Brian K
authors.initials: BK
authors.lastname: Kaspar
mesh_terms: D000818:Animals; D000229:Dependovirus / Q000235:genetics; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics*; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D055435:Myostatin; D012098:Reproduction; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: C525911:MSTN protein, human; C525912:Mstn protein, mouse; D055435:Myostatin; D016212:Transforming Growth Factor beta