A single ascending‐dose study of muscle regulator ace‐031 in healthy volunteers

@article{Attie2013ASA,
  title={A single ascending‐dose study of muscle regulator ace‐031 in healthy volunteers},
  author={Kenneth M. Attie and Niels Geert Borgstein and Yijun Yang and Carolyn H. Condon and Dawn M Wilson and Amelia E. Pearsall and Ravi Kumar and Debbie A Willins and Jasbir S. Seehra and Matthew L. Sherman},
  journal={Muscle \& Nerve},
  year={2013},
  volume={47}
}
ACE‐031 is a soluble form of activin receptor type IIB (ActRIIB). ACE‐031 promotes muscle growth by binding to myostatin and other negative regulators of muscle mass. 

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References

SHOWING 1-10 OF 24 REFERENCES

Administration of a soluble activin type IIB receptor promotes skeletal muscle growth independent of fiber type.

TLDR
Optimism is provided that ACE-031 may be a viable therapeutic in the treatment of musculoskeletal diseases and future studies should be undertaken to confirm that the observed effects are not age dependent or due to the relatively short study duration.

The effects of a soluble activin type IIB receptor on obesity and insulin sensitivity

TLDR
The findings show that disruption of ActRIIB signaling is a viable pharmacological approach for treating obesity and diabetes.

Safety and Efficacy of Teriparatide in Elderly Women with Established Osteoporosis: Bone Anabolic Therapy from a Geriatric Perspective

TLDR
The safety and efficacy of teriparatide in patients aged 75 and older and those of women younger than 75 using data from the Fracture Prevention Trial (FPT) are compared.

A soluble activin receptor type IIb prevents the effects of androgen deprivation on body composition and bone health.

TLDR
It is demonstrated that treatment with ActRIIB-mFc restored muscle mass, adiposity, and bone quality to normal levels in a mouse model of androgen deprivation, thereby alleviating multiple adverse consequences of such therapy.

Myostatin mutation associated with gross muscle hypertrophy in a child.

TLDR
A mutation in the gene for myostatin is described in a child with muscle hypertrophy and unusual strength and greater understanding of muscle growth and maintenance is important for future therapies.

Regulation of muscle growth by multiple ligands signaling through activin type II receptors.

TLDR
A potent myostatin inhibitor, a soluble form of the activin type IIB receptor (ACVR2B), is described, which can cause dramatic increases in muscle mass when injected into wild-type mice.

Pretreatment with a soluble activin type IIB receptor/Fc fusion protein improves hypoxia-induced muscle dysfunction.

TLDR
Data suggest that targeting the ActRIIB is an effective strategy to counter hypoxia-induced muscle dysfunction and to preacclimatize to Hypoxia in clinical or high-altitude settings.

Myostatin propeptide‐mediated amelioration of dystrophic pathophysiology

TLDR
This study demonstrates that pharmacological blockade using a myostatin propeptide stabilized by fusion to IgG‐Fc improved pathophysiology of the mdx mouse model of DMD, and provides a novel pharmacological strategy for treatment of diseases associated with muscle wasting such as DMD.