Abstract
Mice and cattle with mutations in the myostatin (GDF8) gene show a marked increase in body weight and muscle mass, indicating that this new member of the TGF-β superfamily is a negative regulator of skeletal muscle growth. Inhibition of the myostatin gene product is predicted to increase muscle mass and improve the disease phenotype in a variety of primary and secondary myopathies. We tested the ability of inhibition of myostatin in vivo to ameliorate the dystrophic phenotype in the mdx mouse model of Duchenne muscular dystrophy (DMD). Blockade of endogenous myostatin by using intraperitoneal injections of blocking antibodies for three months resulted in an increase in body weight, muscle mass, muscle size and absolute muscle strength in mdx mouse muscle along with a significant decrease in muscle degeneration and concentrations of serum creatine kinase. The functional improvement of dystrophic muscle by myostatin blockade provides a novel, pharmacological strategy for treatment of diseases associated with muscle wasting such as DMD, and circumvents the major problems associated with conventional gene therapy in these disorders.
Original language | English (US) |
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Pages (from-to) | 418-421 |
Number of pages | 4 |
Journal | Nature |
Volume | 420 |
Issue number | 6914 |
DOIs | |
State | Published - Nov 28 2002 |
Externally published | Yes |
Funding
Acknowledgements We thank L. Sweeney, C. Bönnemann, J. Khurana (University of Pennsylvania) and L. Edvinsson (Glostrup Hospital, University of Copenhagen and Lund) for guidance and helpful discussions, and N. Wolfman (Wyeth Research/Genetics Institute) for providing reagents and helpful discussions. T.S.K. was a paid consultant for Wyeth Research/ Genetics Institute during the study. The study was supported in part by a grant from Wyeth Research/Genetics Institute and a predoctoral fellowship to T.O.B.K. from the Faculty of Medicine, Copenhagen University, Denmark. Acknowledgements We thank E. Marban for the gift of the EGFP–IRES–Kir2.1 construct. We also thank the members of our laboratory for discussion. This work was supported by grants from the National Institutes of Health and the NSF. V.N.M. is a Sloan Foundation Fellow, a Pew Scholar, an EJLB Foundation Scholar and a National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator. J.B. is a Grable Investigator of NARSAD.
ASJC Scopus subject areas
- General