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

  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},
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. 

Safety and pharmacokinetics of bimagrumab in healthy older and obese adults with body composition changes in the older cohort

This randomized double‐blind, placebo‐controlled study investigated safety, pharmacokinetics (PK), and pharmacodynamics of bimagrumab in healthy older and obese adults.

Myostatin inhibitors in sports drug testing: Detection of myostatin‐neutralizing antibodies in plasma/serum by affinity purification and Western blotting

The aim of this study was to develop a qualitative detection assay for myostatin‐neutralizing antibodies for doping control purposes by using immunological approaches.

Myostatin inhibitor ACE‐031 treatment of ambulatory boys with Duchenne muscular dystrophy: Results of a randomized, placebo‐controlled clinical trial

ACE‐031 use demonstrated trends for pharmacodynamic effects on lean mass, fat mass, BMD, and 6MWT and myostatin inhibition is a promising therapeutic approach for DMD.

Activin Type II Receptor Blockade for Treatment of Muscle Depletion in Chronic Obstructive Pulmonary Disease. A Randomized Trial

Blocking the action of negative muscle regulators through the activin type II receptors with bimagrumab treatment safely increased skeletal muscle mass but did not improve functional capacity in patients with COPD and low muscle mass.

Are we closer to having drugs to treat muscle wasting disease?

An overview of candidate drugs to treat muscle wasting disease that are available or in development are provided, including ghrelin agonists, selective androgen receptor molecules, megestrol acetate, activin receptor antagonists, espindolol, and fast skeletal muscle troponin inhibitors.

Pharmacological inhibition of myostatin and changes in lean body mass and lower extremity muscle size in patients receiving androgen deprivation therapy for prostate cancer.

Four weekly s.c. doses of AMG 745 were well tolerated and were associated with increased LBM and decreased fat in the men receiving ADT for nonmetastatic prostate cancer, and support further investigation of AMg 745 in clinical settings with muscle loss and atrophy.

Treating cachexia using soluble ACVR2B improves survival, alters mTOR localization, and attenuates liver and spleen responses

Cancer cachexia increases morbidity and mortality, and blocking of activin receptor ligands has improved survival in experimental cancer. However, the underlying mechanisms have not yet been fully

ActRIIB blockade increases force‐generating capacity and preserves energy supply in exercising mdx mouse muscle in vivo

Data support the clinical interest of ActRIIB blockade for reversing dystrophic muscle wasting and increases force‐generating capacity and preserves energy supply in exercising mdx mouse muscle in vivo.

Frailty, sarcopenia, and hormones.

Myostatin/Activin Receptor Ligands in Muscle and the Development Status of Attenuating Drugs

Drugs still in development include antibodies and gene therapeutics, all with different targets and thus, safety, efficacy, and proposed use profiles, which could revolutionize the treatment of both acute and chronic muscle wasting.



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

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

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

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.

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.

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.

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.

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

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.