Therapeutic augmentation of the growth hormone axis to improve outcomes following peripheral nerve injury

Expert Opin Ther Targets. 2016 Oct;20(10):1259-65. doi: 10.1080/14728222.2016.1188079. Epub 2016 May 24.

Abstract

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

Keywords: Chronic denervation; Schwann cell; growth hormone; insulin-like growth factor-1 (IGF-1); muscle atrophy; peripheral nerve injury; peripheral nerve regeneration; tesamorelin.

Publication types

  • Review

MeSH terms

  • Animals
  • Axons
  • Drug Design
  • Growth Hormone / administration & dosage
  • Growth Hormone / metabolism*
  • Humans
  • Nerve Regeneration / physiology*
  • Peripheral Nerve Injuries / drug therapy*
  • Peripheral Nerve Injuries / physiopathology
  • Schwann Cells / pathology

Substances

  • Growth Hormone