Recombinant human neurotrophic factors accelerate colonic transit and relieve constipation in humans

Bernard Coulie, Lawrence A. Szarka, Michael Camilleri, Duane D. Burton, Sanna McKinzie, Nancy Stambler, Jesse M. Cedarbaum

Research output: Contribution to journalArticlepeer-review

133 Scopus citations

Abstract

Background and Aims: The aim of this study was to assess the effects of recombinant human brain-derived neurotrophic factor (r-metHuBDNF) and recombinant human neurotrophic factor 3 (r-metHuNT-3) on gastrointestinal motor functions in healthy people and in patients with constipation. Methods: Gastrointestinal and colonic transit was measured by scintigraphy before and after 2 weeks of treatment. Daily diaries documented symptoms over 6 weeks before, during, and after treatment. In a randomized study of healthy subjects, 40 received 100 μ/kg r-metHuBDNF or placebo subcutaneously (SC) daily. In a separate study, 8 healthy subjects and 8 patients with constipation received 300 μ/kg r-metHuNT-3 SC thrice weekly. Results: r-met- HuBDNF accelerated overall and proximal colonic emptying (P < 0.05) in health, r-metHuNT-3 accelerated overall colonic transit in health and constipation (all P < 0.05) and gastric and small bowel transit (both P < 0.05) in health, r-metHuBDNF tended to increase stool frequency compared with placebo in health (P = 0.09). r-metHuNT-3 increased stool frequency (P = 0.05) and facilitated passage of stool (P < 0.01) in constipated patients. The effects on stool frequency started within 3 days of the beginning of neurotrophin administrations and lasted up to 5 days after treatment ended, r-metHu neurotrophic factors were well tolerated, although half of the participants in the 2 studies developed injection site reactions or paresthesiae. Conclusions: Exogenous neurotrophic factors stimulate human gut motility in health and constipation.

Original languageEnglish (US)
Pages (from-to)41-50
Number of pages10
JournalGastroenterology
Volume119
Issue number1
DOIs
StatePublished - Jul 2000

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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