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On the horizon: trophic peptide growth factors as therapy for neonatal short bowel syndrome
David W Lim1, Paul W Wales2, Justine M Turner3
1a Department of Surgery , University of Alberta , Edmonton , AB , Canada.
Insights
Short bowel syndrome (SBS) in neonates lacks targeted therapies. Peptide growth factors like glucagon-like peptide-2 show promise for stimulating intestinal adaptation in preclinical models.
Area of Science:
- Neonatology
- Gastroenterology
- Pediatric Surgery
Background:
- Short bowel syndrome (SBS) is a significant condition in neonates.
- Current therapeutic options for neonatal SBS are limited, with no approved agents to promote intestinal adaptation.
Purpose of the Study:
- To review short bowel syndrome (SBS) and intestinal adaptation in neonates.
- To explore candidate peptide growth factors, including glucagon-like peptide-2 (GLP-2), insulin-like growth factor-1 (IGF-1), and epidermal growth factor (EGF), as potential therapies for neonatal SBS.
Main Methods:
- Review of existing literature on SBS and intestinal adaptation.
- Discussion of the physiology and roles of candidate peptide growth factors in gastrointestinal development and adaptation.
- Examination of preclinical data on peptide administration in neonatal SBS models.
Main Results:
- Candidate peptides, particularly GLP-2, demonstrate potential to enhance intestinal adaptation in preclinical SBS models.
- Understanding of the physiological roles of GLP-2, IGF-1, and EGF in neonatal gastrointestinal ontogeny is discussed.
Conclusions:
- Clinical application of trophic peptide therapies for neonatal SBS faces challenges, including optimal dosing, timing, and administration routes.
- Trophic peptides show promise in preclinical settings and may offer significant benefits for neonates with irreversible intestinal failure, especially those lacking remnant ileum.
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.
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