Follistatin-based ligand trap ACE-083 induces localized hypertrophy of skeletal muscle with functional improvement in models of neuromuscular disease.

Skeletal muscle is under inhibitory homeostatic regulation by multiple ligands of the transforming growth factor-β (TGFβ) superfamily. Follistatin is a secreted protein that promotes muscle growth and function by sequestering these ligands extracellularly. In the present study, we evaluated the potential of ACE-083 - a locally acting, follistatin-based fusion protein - as a novel therapeutic agent for focal or asymmetric myopathies.

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

Androgen deprivation, a consequence of hypogonadism, certain cancer treatments, or normal aging in men, leads to loss of muscle mass, increased adiposity, and osteoporosis. In the present study, using a soluble chimeric form of activin receptor type IIB (ActRIIB) we sought to offset the adverse effects of androgen deprivation on muscle, adipose tissue, and bone. Castrated (ORX) or sham-operated (SHAM) mice received either TBS [vehicle-treated (VEH)] or systemic administration of ActRIIB-mFc, a soluble fusion protein comprised of a form of the extracellular domain of ActRIIB fused to a murine IgG2aFc subunit.

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

This is the first report that inhibition of negative regulators of skeletal muscle by a soluble form of activin type IIB receptor (ACE-031) increases muscle mass independent of fiber-type expression. This finding is distinct from the effects of selective pharmacological inhibition of myostatin (GDF-8), which predominantly targets type II fibers. In our study 8-wk-old C57BL/6 mice were treated with ACE-031 or vehicle control for 28 days.

Social stress enhances allergen-induced airway inflammation in mice and inhibits corticosteroid responsiveness of cytokine production.

Chronic psychosocial stress exacerbates asthma, but the underlying mechanisms remain poorly understood. We hypothesized that psychosocial stress aggravates allergic airway inflammation by altering innate immune cell function. The effects of stress on airway inflammation, lung function, and glucocorticoid responsiveness were studied in a novel in vivo murine model of combined social disruption stress and allergic sensitization.