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Follistatin: a novel therapeutic for the improvement of muscle regeneration

Abstract

Follistatin (FST) is a member of the TGFβ family and is a secreted glycoprotein that antagonizes many members of the family including Activin A, GDF11 and myostatin. The objective of this study was to explore the use of an engineered Follistatin therapeutic created by fusing FST315 lacking heparin binding activity to the N-terminus of a murine IgG1 Fc (FST315-ΔHBS-Fc) as a systemic therapeutic agent in models of muscle injury. Systemic administration of this molecule was found to increase body weight and lean muscle mass after weekly administration in normal mice. Subsequently, we tested this agent in several models of muscle injury which were chosen based on their severity of damage and their ability to reflect clinical settings. FST315-ΔHBS-Fc treatment proved to be a potent inducer of muscle remodeling and regeneration. FST315-ΔHBS-Fc induced improvements in muscle repair after injury/atrophy by modulating the early inflammatory phase allowing for increased macrophage density, and Pax7-positive cells leading to an accelerated restoration of myofibers and muscle function. Collectively, these data demonstrate the benefits of a therapeutically viable form of FST that can be leveraged as an alternate means of ameliorating muscle regeneration.

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Alex's notes: We all suffer injury to our muscles, whether it be self-inflicted from heavy resistance training, trauma (falls or collisions in contact sports), or genetic disorders (muscular dystrophy). For those of you familiar with myostatin, the grand inhibitor of muscle growth, FST acts through a similar albeit opposite mechanism. In fact, FST inhibits the effects of myostatin. As the study at hand mentions, this makes FST a novel theraputic agent for many injuries and disorders of muscle tissue, and the study confirms its use in mice. I am looking forward to future applications and human trials.

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