Long-term enhancement of skeletal muscle mass and strength by single gene administration of myostatin inhibitors.
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.
Haidet
Amanda M
AM
The Research Institute, Nationwide Children's Hospital, Columbus, OH 43205, USA.
Rizo
Liza
L
Handy
Chalonda
C
Umapathi
Priya
P
Eagle
Amy
A
Shilling
Chris
C
Boue
Daniel
D
Martin
Paul T
PT
Sahenk
Zarife
Z
Mendell
Jerry R
JR
Kaspar
Brian K
BK
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*
C525911:MSTN protein, human; C525912:Mstn protein, mouse; D055435:Myostatin; D016212:Transforming Growth Factor beta