Recombinant human neurotrophic factors accelerate colonic transit and relieve constipation in humans.
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.
Coulie
B
B
Gastroenterology Research Unit, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA.
Szarka
L A
LA
Camilleri
M
M
Burton
D D
DD
McKinzie
S
S
Stambler
N
N
Cedarbaum
J M
JM
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
D019208:Brain-Derived Neurotrophic Factor; D004043:Dietary Fiber; D009414:Nerve Growth Factors; D011994:Recombinant Proteins; C109458:r-metHuBDNF protein, recombinant