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

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
• short bowel syndrome
• intestinal failure
• glucagon-like peptide-2
• teduglutide
• insulin-like growth factor
• epidermal growth factor
• growth factors

Article Highlights

• SBS and consequent intestinal failure occur more frequently in neonates and children, and diseases leading to SBS in neonates often require removal of ileum.

• Unlike adults, there are currently no approved therapies aimed at stimulating intestinal adaptation in children with SBS.

• Intestinotrophic peptides, such as GLP-2, IGF-1, and EGF, have shown therapeutic benefit in preclinical models of adult SBS.

• The limited preclinical studies investigating the potential efficacy of trophic peptide therapies in neonatal SBS show promise with GLP-2 therapy, notably in SBS without remnant ileum.

• The clinical translation of trophic peptide therapies targeted for neonates and children with SBS will require the determination of the ideal growth factor or a combination of growth factors, and of the optimal dose, route, and timing of administration.

• Trophic peptides may become an important option for neonates with SBS that lack remnant ileum and are most at risk for irreversible intestinal failure.

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Financial and competing interests disclosure

Studies on GLP-2 in neonatal piglets in the Turner/Wales lab are supported by an operating grant from the CIHR (MOP-126179). Studies on EGF in neonatal piglets in the Turner/Wales lab are supported in part by the American Society of Parenteral and Enteral Nutrition Rhoads Research Foundation. Studies on GLP-2 and EGF in neonatal piglets are further supported by the Edmonton Civic Employees Charitable Assistance Fund. DWL is supported by a Doctoral Research Award from the CIHR, a Clinician Fellowship from Alberta Innovates - Health Solutions, a Graduate Studentship from the Women and Children’s Health Research Institute through the generous support of the Stollery Children’s Hospital Foundation, and an Honorary Izaak Walton Killam Memorial Scholarship from the Killam Trusts and the University of Alberta Faculty of Graduate Studies and Research. PLB is supported by the Canada Research Chairs program.