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Follistatin, by antagonism of myostatin and activin, which are negative regulators of skeletal muscle and inflammatory response, is a promising therapeutic target for Duchenne Muscular Dystrophy. In this study, we constructed a quantitative systems pharmacology model for FS\u2010EEE\u2010Fc, a follistatin recombinant protein to investigate its efficacy from dual target binding, and, subsequently, to project its human efficacious dose. Based on model simulations, with an assumed efficacy threshold of 7\u201310% muscle volume increase, 3\u20135\u00a0mg\/kg weekly dosing of FS\u2010EEE\u2010Fc is predicted to achieve meaningful clinical outcome. In conclusion, the study demonstrated an application of mechanism driven approach at early stage of a rare disease drug development to support lead compound optimization, enable human dose, pharmacokinetics, and efficacy predictions.<\/jats:p>","DOI":"10.1002\/psp4.12518","type":"journal-article","created":{"date-parts":[[2020,5,18]],"date-time":"2020-05-18T05:32:52Z","timestamp":1589779972000},"page":"342-352","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Leveraging Quantitative Systems Pharmacology Approach into Development of Human Recombinant Follistatin Fusion Protein for Duchenne Muscular Dystrophy"],"prefix":"10.1002","volume":"9","author":[{"given":"Hoa Q.","family":"Nguyen","sequence":"first","affiliation":[{"name":"Shire HGT, Inc. 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