title: Recombinant human neurotrophic factors accelerate colonic transit and relieve constipation in humans.
abstract: OBJECTIVE
  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 microg/kg r-metHuBDNF or placebo subcutaneously (SC) daily. In a separate study, 8 healthy subjects and 8 patients with constipation received 300 microg/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.
authors.affiliation: Gastroenterology Research Unit, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA.
authors.forename: B
authors.initials: B
authors.lastname: Coulie
authors.forename: L A
authors.initials: LA
authors.lastname: Szarka
authors.forename: M
authors.initials: M
authors.lastname: Camilleri
authors.forename: D D
authors.initials: DD
authors.lastname: Burton
authors.forename: S
authors.initials: S
authors.lastname: McKinzie
authors.forename: N
authors.initials: N
authors.lastname: Stambler
authors.forename: J M
authors.initials: JM
authors.lastname: Cedarbaum
mesh_terms: D000328:Adult; D019208:Brain-Derived Neurotrophic Factor / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003106:Colon / Q000000981:diagnostic imaging / Q000378:metabolism*; D003248:Constipation / Q000188:drug therapy* / Q000503:physiopathology; D003672:Defecation / Q000187:drug effects; D004043:Dietary Fiber / Q000008:administration & dosage; D005260:Female; D005772:Gastrointestinal Transit / Q000187:drug effects*; D006801:Humans; D007279:Injections, Subcutaneous / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000187:drug effects / Q000627:therapeutic use*; D011877:Radionuclide Imaging; D011994:Recombinant Proteins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D012016:Reference Values
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D004043:Dietary Fiber; D009414:Nerve Growth Factors; D011994:Recombinant Proteins; C109458:r-metHuBDNF protein, recombinant