PT  - JOURNAL ARTICLE
AU  - Yaden, Benjamin C.
AU  - Croy, Johnny E.
AU  - Wang, Yan
AU  - Wilson, Jonathan M.
AU  - Datta-Mannan, Amita
AU  - Shetler, Pamela
AU  - Milner, Andrea
AU  - Bryant, Henry U.
AU  - Andrews, Jessica
AU  - Dai, Guoli
AU  - Krishnan, Venkatesh
TI  - Follistatin: A Novel Therapeutic for the Improvement of Muscle Regeneration
AID  - 10.1124/jpet.113.211169
DP  - 2014 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 355--371
VI  - 349
IP  - 2
4099  - http://jpet.aspetjournals.org/content/349/2/355.short
4100  - http://jpet.aspetjournals.org/content/349/2/355.full
SO  - J Pharmacol Exp Ther2014 May 01; 349
AB  - Follistatin (FST) is a member of the tissue growth factor β family and is a secreted glycoprotein that antagonizes many members of the family, including activin A, growth differentiation factor 11, 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.