title: Therapeutic augmentation of the growth hormone axis to improve outcomes following peripheral nerve injury.
abstract: BACKGROUND
  Peripheral nerve injuries often result in debilitating motor and sensory deficits. There are currently no therapeutic agents that are clinically available to enhance the regenerative process. Following surgical repair, axons often must regenerate long distances to reach and reinnervate distal targets. Progressive atrophy of denervated muscle and Schwann cells (SCs) prior to reinnervation contributes to poor outcomes. Growth hormone (GH)-based therapies have the potential to accelerate axonal regeneration while at the same time limiting atrophy of muscle and the distal regenerative pathway prior to reinnervation.
  
  
  METHODS
  In this review, we discuss the potential mechanisms by which GH-based therapies act on the multiple tissue types involved in peripheral nerve regeneration to ultimately enhance outcomes, and review the pertinent mechanistic and translational studies that have been performed. We also address potential secondary benefits of GH-based therapies pertaining to improved bone, tendon and wound healing in the setting of peripheral nerve injury.
  
  
  CONCLUSIONS
  GH-based therapies carry great promise for the treatment of peripheral nerve injuries, given the multi-modal mechanism of action not seen with other experimental therapies. A number of FDA-approved drugs that augment the GH axis are currently available, which may facilitate clinical translation.
authors.affiliation: a Department of Plastic and Reconstructive Surgery , Johns Hopkins University School of Medicine , Baltimore , MD , USA.
authors.forename: Sami H
authors.initials: SH
authors.lastname: Tuffaha
authors.affiliation: a Department of Plastic and Reconstructive Surgery , Johns Hopkins University School of Medicine , Baltimore , MD , USA.
authors.forename: Prateush
authors.initials: P
authors.lastname: Singh
authors.affiliation: a Department of Plastic and Reconstructive Surgery , Johns Hopkins University School of Medicine , Baltimore , MD , USA.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Budihardjo
authors.affiliation: b The Curtis National Hand Center , Baltimore , MD , USA.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Means
authors.affiliation: b The Curtis National Hand Center , Baltimore , MD , USA.
authors.forename: James P
authors.initials: JP
authors.lastname: Higgins
authors.affiliation: a Department of Plastic and Reconstructive Surgery , Johns Hopkins University School of Medicine , Baltimore , MD , USA.
authors.forename: Jaimie T
authors.initials: JT
authors.lastname: Shores
authors.affiliation: c Department of Medicine , Division of Endocrinology, Johns Hopkins University School of Medicine , Baltimore , MD , USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Salvatori
authors.affiliation: d Department of Neurology , Johns Hopkins University School of Medicine , Baltimore , MD , USA.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Höke
authors.affiliation: a Department of Plastic and Reconstructive Surgery , Johns Hopkins University School of Medicine , Baltimore , MD , USA.
authors.forename: W P Andrew
authors.initials: WP
authors.lastname: Lee
authors.affiliation: a Department of Plastic and Reconstructive Surgery , Johns Hopkins University School of Medicine , Baltimore , MD , USA.
authors.forename: Gerald
authors.initials: G
authors.lastname: Brandacher
mesh_terms: D000818:Animals; D001369:Axons; D015195:Drug Design; D013006:Growth Hormone / Q000008:administration & dosage / Q000378:metabolism*; D006801:Humans; D009416:Nerve Regeneration / Q000502:physiology*; D059348:Peripheral Nerve Injuries / Q000188:drug therapy* / Q000503:physiopathology; D012583:Schwann Cells / Q000473:pathology
chemical_list: D013006:Growth Hormone
keywords: Chronic denervation; Schwann cell; growth hormone; insulin-like growth factor-1 (IGF-1); muscle atrophy; peripheral nerve injury; peripheral nerve regeneration; tesamorelin