On the horizon: trophic peptide growth factors as therapy for neonatal short bowel syndrome

Expert Opin Ther Targets. 2016 Jul;20(7):819-30. doi: 10.1517/14728222.2016.1146695. Epub 2016 Mar 1.

Abstract

Introduction: Short bowel syndrome (SBS) occurs more commonly in human neonates than in adults. There are currently no approved therapeutic agents aimed directly at stimulating intestinal adaptation in this population.

Areas covered: A brief review of SBS and intestinal adaptation is first presented. We then present candidate peptide growth factors that are suggested to augment intestinal adaptation in SBS, with a particular focus on glucagon-like peptide-2, as well as insulin-like growth factor-1 and epidermal growth factor. The normal physiology of these peptides and our understanding of their roles in intestinal adaptation are discussed. We further consider the roles of these peptides in the ontogeny of the gastrointestinal tract and we present the limited preclinical data on the effects of administering these peptides in neonatal SBS.

Expert opinion: The clinical translation of trophic peptide therapies in neonatal SBS will require several challenges to be overcome. The optimal dose, timing and route of administration for the likely peptide, or combination of peptides, to be administered will be paramount. Despite their cost to patient care, trophic peptides have shown promise in preclinical models of neonatal SBS and may be especially beneficial for neonates that lack remnant ileum and suffer from irreversible intestinal failure.

Keywords: Neonatal; epidermal growth factor; glucagon-like peptide-2; growth factors; insulin-like growth factor; intestinal failure; short bowel syndrome; teduglutide.

Publication types

  • Review

MeSH terms

  • Adaptation, Physiological
  • Adult
  • Animals
  • Drug Design
  • Epidermal Growth Factor / administration & dosage
  • Epidermal Growth Factor / metabolism
  • Glucagon-Like Peptide 2 / administration & dosage
  • Glucagon-Like Peptide 2 / metabolism
  • Humans
  • Infant, Newborn
  • Insulin-Like Growth Factor I / administration & dosage
  • Insulin-Like Growth Factor I / metabolism
  • Intercellular Signaling Peptides and Proteins / administration & dosage*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Peptides / administration & dosage*
  • Peptides / metabolism
  • Short Bowel Syndrome / drug therapy*
  • Short Bowel Syndrome / physiopathology

Substances

  • Glucagon-Like Peptide 2
  • IGF1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • Peptides
  • Epidermal Growth Factor
  • Insulin-Like Growth Factor I