title: Follistatin Gene Therapy Improves Ambulation in Becker Muscular Dystrophy.
abstract: Follistatin is a ubiquitous secretory propeptide that functions as a potent inhibitor of the myostatin pathway, resulting in an increase in skeletal muscle mass. Its ability to interact with the pituitary activin-inhibin axis and suppress the secretion of follicle-stimulating hormone (FSH) called for caution in its clinical applicability. This limitation was circumvented by the use of one of the alternatively spliced follistatin variants, FS344, undergoing post-translational modification to FS315. This follistatin isoform is serum-based, and has a 10-fold lower affinity to activin compared to FS288. Preclinical studies of intramuscular delivery of the follistatin gene demonstrated safety and efficacy in enhancing muscle mass. We herein review the evidence supporting the utility of follistatin as a genetic enhancer to improve cellular performance. In addition, we shed light on the results of the first clinical gene transfer trial using the FS344 isoform of follistatin in subjects with Becker muscular dystrophy as well as the future directions for clinical gene therapy trials using follistatin.
authors.affiliation: Department of Pediatrics, Division of Neurology and Neuromuscular, The Ohio State University, Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Samiah A
authors.initials: SA
authors.lastname: Al-Zaidy
authors.affiliation: Department of Pediatrics, Division of Neurology and Neuromuscular, The Ohio State University, Nationwide Children's Hospital, Columbus, OH, USA.|Department of Neurology, The Ohio State University, Nationwide Children's Hospital, OH, USA.|Center for Gene Therapy, Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Zarife
authors.initials: Z
authors.lastname: Sahenk
authors.affiliation: Department of Pediatrics, Division of Neurology and Neuromuscular, The Ohio State University, Nationwide Children's Hospital, Columbus, OH, USA.|Center for Gene Therapy, Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Louise R
authors.initials: LR
authors.lastname: Rodino-Klapac
authors.affiliation: Department of Pediatrics, Division of Neurology and Neuromuscular, The Ohio State University, Nationwide Children's Hospital, Columbus, OH, USA.|Department of Neurology, The Ohio State University, Nationwide Children's Hospital, OH, USA.|Center for Gene Therapy, Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Kaspar
authors.affiliation: Department of Pediatrics, Division of Neurology and Neuromuscular, The Ohio State University, Nationwide Children's Hospital, Columbus, OH, USA.|Department of Neurology, The Ohio State University, Nationwide Children's Hospital, OH, USA.|Center for Gene Therapy, Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Jerry R
authors.initials: JR
authors.lastname: Mendell
keywords: Becker muscular dystrophy; FS344; Follistatin; gene therapy; myostatin