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

Background & Aims: The aim of this study was to assess the effects of recom binant human brainderived neurotrophic factor (r-metHuBDNF) and recombinant human neurotrophic factor 3 (r-metHuNT-3) on gastrointestinal motor functi ons in healthy people and in patients with constipation. Methods: Gastroint estinal 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 mu g/kg r-metHuBDNF or placebo subcutaneously (SC) daily. In a separate study, 8 healthy subjects and 8 patients with constipation recei ved 300 mu g/kg r-metHuNT-3 SC thrice weekly. Results: r-met-HuBDNF acceler ated overall and proximal colonic emptying (P < 0.05) in health. r-metHuNT- 3 accelerated overall colonic transit in health and constipation tall P < 0 .05) and gastric and small bower transit (both P < 0.05) in health. r-metHu BDNF tended to increase stool frequency compared with placebo in health (P = 0.09), r-metHuNT-3 increased stool frequency (P = 0.05) and facilitated p assage of stool (P < 0.01) in constipated patients. The effects on stool fr equency started within 3 days of the beginning of neurotrophin administrati ons and lasted up to 5 days after treatment ended. r-metHu neurotrophic fac tors were well tolerated, although half of the participants in the 2 studie s developed injection site reactions or paresthesiae. Conclusions: Exogenou s neurotrophic factors stimulate human gut motility in health and constipat ion.