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The Role of ActRIIB Signaling and Muscle Growth. Muscle growth is regulated by proteins in the TGF-? protein superfamily that serve as ‘on’ or ‘off’ switches for muscle production. Several molecules including GDF-8 interact with the ActRIIB receptor and send an ‘off’ signal to stop muscle production. In the absence of these ‘off’ switch molecules that signal through the ActRIIB receptor, muscle mass increases dramatically. Decreased ActRIIB Signaling Results in Muscle Growth. In nature, this effect has been observed in numerous species, particularly in animals that have been bred for increased musculature and strength. For example, Belgian Blue cattle lack the gene for GDF-8, which is one of several molecules that activate the ActRIIB receptor. A deficiency of this protein results in cattle with tremendously developed musculature and strength. Similar effects have been observed in other species, including rodents, dogs and even humans, sustaviron 250 mg injectable steroids sustanon (testosterone blend). Treatment with ACE-031 Builds Skeletal Muscle. Treatment with ACE-031 promotes muscle growth by inhibiting ActRIIB signaling. ACE-031 binds to proteins that signal through the ActRIIB receptor to limit muscle growth. When ACE-031 binds to these proteins, it prevents them from interacting with the ActRIIB receptor, thus allowing muscle to grow. Moreover, because ACE-031 prevents GDF-8 and other proteins that regulate muscle mass from signaling through the ActRIIB receptor, its effects on lean muscle exceed those of inhibitors of GDF-8 (myostatin) alone. Non-Clinical Results: When animals are treated with ACE-031, they experience growth in lean muscle and are considerably stronger than their untreated counterparts. This has been shown in several species, and in both healthy animals and in animals with diseases associated with muscle weakness and wasting. Clinical Results: Single Ascending Dose Phase 1 Study ‘ Acceleron completed a clinical study of ACE-031 (A031-01) in 48 healthy postmenopausal women. These subjects received a single dose of ACE-031 across a range of dose levels. For a description of the study design, click here. For the poster presentation of the study results click here and click here for the accompanying press release. At higher doses, the effects of ACE-031 on skeletal muscle were encouraging. After a single dose of ACE-031, subjects developed roughly 1 kilogram (over 2 pounds) of muscle at 2 weeks. Moreover, ACE-031 altered biomarkers of fat metabolism (increased adiponectin and decreased leptin) and bone formation and resorption (increased BSAP and decreased CTX) at single doses of 1 and 3 mg/kg. ACE-031 was generally well-tolerated at all dose levels. No serious adverse events were observed.
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