Mammalian-cell-produced neurturin (NTN) is more potent than purified Escherichia coli-produced NTN.
Neurturin (NTN) is a recently identified homologue of glial-cell-line-derived neurotrophic factor. Both factors promote the survival of dopaminergic (DA) neurons. We investigated the biological activity of mammalian-cell-produced NTN versus purified Escherichia coli-produced NTN. Baby hamster kidney cells were engineered to stably secrete mature human NTN. Mammalian-cell-derived NTN enhanced the activity of embryonic DA neurons in vitro, with greater potency (maximum effect achieved in the picogram range) than purified E. coli-produced NTN. Cell-based delivery of NTN (less than 10 ng/day) was also shown to be biologically active in vivo. These results suggest that mammalian-cell-derived NTN, synthesized de novo and delivered in small quantities to the parenchyma at the target site, may be as active as much larger quantities of purified, E. coli-produced NTN, delivered by other means.
Hoane
M R
MR
CytoTherapeutics, Inc., 701 George Washington Highway Lincoln, Rhode Island, 02865, USA.
Puri
K D
KD
Xu
L
L
Stabila
P F
PF
Zhao
H
H
Gulwadi
A G
AG
Phillips
H S
HS
Devaux
B
B
Lindner
M D
MD
Tao
W
W
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001681:Biological Assay; D002214:Capsules; D018929:Cell Culture Techniques / Q000379:methods; D002470:Cell Survival / Q000187:drug effects; D017690:Cell Transplantation; D002478:Cells, Cultured; D002552:Cerebral Ventricles; D003342:Corpus Striatum; D006224:Cricetinae; D017077:Culture Media, Conditioned / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D004926:Escherichia coli / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D007668:Kidney / Q000166:cytology*; D008297:Male; D008322:Mammals; D009414:Nerve Growth Factors / Q000235:genetics* / Q000302:isolation & purification / Q000494:pharmacology*; D051101:Neurturin; D051381:Rats; D017207:Rats, Sprague-Dawley; D012399:Rotation; D014162:Transfection
D002214:Capsules; D017077:Culture Media, Conditioned; D018491:Dopamine Agonists; C495053:NRTN protein, human; D009414:Nerve Growth Factors; D051101:Neurturin; C495057:Nrtn protein, rat; D001058:Apomorphine