Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Mar 3;10(3):533.
doi: 10.3390/cells10030533.

Antimyostatin Treatment in Health and Disease: The Story of Great Expectations and Limited Success

Tue L Nielsen  1 , John Vissing  1 , Thomas O Krag  1
Affiliations
Review

Antimyostatin Treatment in Health and Disease: The Story of Great Expectations and Limited Success

Tue L Nielsen et al. Cells. .

Abstract

In the past 20 years, myostatin, a negative regulator of muscle mass, has attracted attention as a potential therapeutic target in muscular dystrophies and other conditions. Preclinical studies have shown potential for increasing muscular mass and ameliorating the pathological features of dystrophic muscle by the inhibition of myostatin in various ways. However, hardly any clinical trials have proven to translate the promising results from the animal models into patient populations. We present the background for myostatin regulation, clinical and preclinical results and discuss why translation from animal models to patients is difficult. Based on this, we put the clinical relevance of future antimyostatin treatment into perspective.

Keywords: ActRIIB; TGF-β; muscular dystrophy; muscular regeneration; myostatin.

PubMed Disclaimer

Conflict of interest statement

T.L.N. declares no conflicts of interest. T.O.K. has served as a consultant for Asklepios Biopharmaceuticals. J.V. has received research and travel support, and/or speaker honoraria from Sanofi/Genzyme and Alexion Pharmaceuticals, and served on advisory boards or as a consultant for Roche, Asklepios Biopharmaceuticals, PTC Therapeutics, Sanofi/Genzyme, Santhera Pharmaceuticals, Sarepta Therapeutics, Novartis Pharma AG, Audentes Therapeutics and Stealth Biotherapeutics.

Figures

Figure 1
Figure 1
An overview of various approaches used in myostatin inhibition. Various factors and approaches in myostatin inhibition as outlined in Section 2 and Section 5. Treatments applied in clinical trials have been colored yellow. The Smad2/3 intracellular signaling pathway downstream the ActRIIB leads to altered gene transcription of muscle regulatory factors.
See this image and copyright information in PMC

References

    1. McPherron A.C., Lawler A.M., Lee S.-J. Regulation of Skeletal Muscle Mass in Mice by a New TGF-p Superfamily Member. Nature. 1997;387:83–90. doi: 10.1038/387083a0. - DOI - PubMed
    1. Grobet L., Martin L.J., Poncelet D., Pirottin D., Brouwers B., Riquet J., Schoeberlein A., Dunner S., Ménissier F., Massabanda J., et al. A Deletion in the Bovine Myostatin Gene Causes the Double-Muscled Phenotype in Cattle. Nat. Genet. 1997;17:71–74. doi: 10.1038/ng0997-71. - DOI - PubMed
    1. Kambadur R., Sharma M., Smith T.P., Bass J.J. Mutations in Myostatin (GDF8) in Double-Muscled Belgian Blue and Piedmontese Cattle. Genome Res. 1997;7:910–916. doi: 10.1101/gr.7.9.910. - DOI - PubMed
    1. McPherron A.C., Lee S.J. Double Muscling in Cattle Due to Mutations in the Myostatin Gene. Proc. Natl. Acad. Sci. USA. 1997;94:12457–12461. doi: 10.1073/pnas.94.23.12457. - DOI - PMC - PubMed
    1. Mosher D.S., Quignon P., Bustamante C.D., Sutter N.B., Mellersh C.S., Parker H.G., Ostrander E.A. A Mutation in the Myostatin Gene Increases Muscle Mass and Enhances Racing Performance in Heterozygote Dogs. PLoS Genet. 2007;3 doi: 10.1371/journal.pgen.0030079. - DOI - PMC - PubMed

LinkOut - more resources