Long-term delivery of nerve growth factor by encapsulated cell biodelivery in the Göttingen minipig basal forebrain.
Nerve growth factor (NGF) prevents cholinergic degeneration in Alzheimer's disease (AD) and improves memory in AD animal models. In humans, the safe delivery of therapeutic doses of NGF is challenging. For clinical use, we have therefore developed an encapsulated cell (EC) biodelivery device, capable of local delivery of NGF. The clinical device, named NsG0202, houses an NGF-secreting cell line (NGC-0295), which is derived from a human retinal pigment epithelial (RPE) cell line, stably genetically modified to secrete NGF. Bioactivity and correct processing of NGF was confirmed in vitro. NsG0202 devices were implanted in the basal forebrain of Göttingen minipigs and the function and retrievability were evaluated after 7 weeks, 6 and 12 months. All devices were implanted and retrieved without associated complications. They were physically intact and contained a high number of viable and NGF-producing NGC-0295 cells after explantation. Increased NGF levels were detected in tissue surrounding the devices. The implants were well tolerated as determined by histopathological brain tissue analysis, blood analysis, and general health status of the pigs. The NsG0202 device represents a promising approach for treating the cognitive decline in AD patients.
Fjord-Larsen
Lone
L
Functional Biology, NsGene A/S, Ballerup, Denmark. lfl@nsgene.dk
Kusk
Philip
P
Tornøe
Jens
J
Juliusson
Bengt
B
Torp
Malene
M
Bjarkam
Carsten R
CR
Nielsen
Mette S
MS
Handberg
Aase
A
Sørensen
Jens Christian H
JC
Wahlberg
Lars U
LU
D000544:Alzheimer Disease / Q000188:drug therapy*; D000818:Animals; D002214:Capsules; D002460:Cell Line / Q000637:transplantation; D016503:Drug Delivery Systems; D006801:Humans; D020932:Nerve Growth Factor / Q000008:administration & dosage / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use; D016548:Prosencephalon / Q000187:drug effects*; D012160:Retina / Q000166:cytology; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors
D002214:Capsules; D018696:Neuroprotective Agents; D020932:Nerve Growth Factor