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A mouse anti-myostatin antibody increases muscle mass and improves muscle strength and contractility in the mdx mouse model of Duchenne muscular dystrophy and its humanized equivalent, domagrozumab (PF…

Overview of attention for article published in Skeletal Muscle, November 2017
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  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (75th percentile)
  • Average Attention Score compared to outputs of the same age and source

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13 X users

Citations

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88 Mendeley
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Title
A mouse anti-myostatin antibody increases muscle mass and improves muscle strength and contractility in the mdx mouse model of Duchenne muscular dystrophy and its humanized equivalent, domagrozumab (PF-06252616), increases muscle volume in cynomolgus monkeys
Published in
Skeletal Muscle, November 2017
DOI 10.1186/s13395-017-0141-y
Pubmed ID
Authors

Michael St. Andre, Mark Johnson, Prashant N. Bansal, Jeremy Wellen, Andrew Robertson, Alan Opsahl, Peter M. Burch, Peter Bialek, Carl Morris, Jane Owens

Abstract

The treatments currently approved for Duchenne muscular dystrophy (DMD), a progressive skeletal muscle wasting disease, address the needs of only a small proportion of patients resulting in an urgent need for therapies that benefit all patients regardless of the underlying mutation. Myostatin is a member of the transforming growth factor-β (TGF-β) family of ligands and is a negative regulator of skeletal muscle mass. Loss of myostatin has been shown to increase muscle mass and improve muscle function in both normal and dystrophic mice. Therefore, myostatin blockade via a specific antibody could ameliorate the muscle weakness in DMD patients by increasing skeletal muscle mass and function, thereby reducing patients' functional decline. A murine anti-myostatin antibody, mRK35, and its humanized analog, domagrozumab, were developed and their ability to inhibit several TGB-β ligands was measured using a cell-based Smad-activity reporter system. Normal and mdx mice were treated with mRK35 to examine the antibody's effect on body weight, lean mass, muscle weights, grip strength, ex vivo force production, and fiber size. The humanized analog (domagrozumab) was tested in non-human primates (NHPs) for changes in skeletal muscle mass and volume as well as target engagement via modulation of circulating myostatin. Both the murine and human antibodies are specific and potent inhibitors of myostatin and GDF11. mRK35 is able to increase body weight, lean mass, and muscle weights in normal mice. In mdx mice, mRK35 significantly increased body weight, muscle weights, grip strength, and ex vivo force production in the extensor digitorum longus (EDL) muscle. Further, tibialis anterior (TA) fiber size was significantly increased. NHPs treated with domagrozumab demonstrated a dose-dependent increase in lean mass and muscle volume and exhibited increased circulating levels of myostatin demonstrating target engagement. We demonstrated that the potent anti-myostatin antibody mRK35 and its clinical analog, domagrozumab, were able to induce muscle anabolic activity in both rodents, including the mdx mouse model of DMD, and non-human primates. A Phase 2, potentially registrational, clinical study with domagrozumab in DMD patients is currently underway.

X Demographics

X Demographics

The data shown below were collected from the profiles of 13 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 88 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 88 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 17 19%
Student > Ph. D. Student 11 13%
Student > Bachelor 11 13%
Other 7 8%
Student > Master 7 8%
Other 13 15%
Unknown 22 25%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 25 28%
Medicine and Dentistry 13 15%
Agricultural and Biological Sciences 7 8%
Nursing and Health Professions 4 5%
Pharmacology, Toxicology and Pharmaceutical Science 4 5%
Other 9 10%
Unknown 26 30%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 7. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 December 2017.
All research outputs
#4,541,121
of 23,007,887 outputs
Outputs from Skeletal Muscle
#130
of 364 outputs
Outputs of similar age
#82,489
of 331,173 outputs
Outputs of similar age from Skeletal Muscle
#5
of 10 outputs
Altmetric has tracked 23,007,887 research outputs across all sources so far. Compared to these this one has done well and is in the 80th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 364 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.2. This one has gotten more attention than average, scoring higher than 64% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 331,173 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 75% of its contemporaries.
We're also able to compare this research output to 10 others from the same source and published within six weeks on either side of this one. This one has scored higher than 5 of them.