Human follistatin is a regulatory glycoprotein with widespread biological functions and promise for potential clinical applications. To better define the pharmacokinetic/pharmacodynamic relationship, in-depth studies and analyses of the native follistatin-315 were conducted. These studies demonstrated that follistatin-315 was poorly suited for acting as a parenterally administered biotherapeutic. Therefore, the native molecule was modified by fusing follistatin-315 to murine IgG1 Fc and removing the intrinsic heparan binding activity of follistatin. The engineered variant had ∼100- and ∼1600-fold improvements in terminal half-life and exposure, respectively. In addition, the variant showed a dose-dependent pharmacological effect when administered subcutaneously in a model of muscle atrophy.
See article at J Pharmacol Exp Ther 2013 344:616–623.
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