The Open Tissue Engineering and Regenerative Medicine Journal

2012, 5 : 35-42
Published online 2012 May 18. DOI: 10.2174/1875043501205010035
Publisher ID: TOTERMJ-5-35

Encapsulated Cell Biodelivery of Transposon-Mediated High-Dose NGF to the Göttingen Mini Pig Basal Forebrain

Lone Fjord-Larsen , Philip Kusk , Malene Torp , Jens Christian H. Sorensen , Kaare Ettrup , Carsten R. Bjarkam , Jens Tornoe , Bengt Juliusson and Lars U. Wahlberg
NsGene A/S, Baltorpvej 154, DK-2750 Ballerup, Denmark.

ABSTRACT

Nerve Growth Factor (NGF) has therapeutic effects on the cholinergic neurodegeneration in Alzheimer's disease (AD). We have previously described an implantable Encapsulated Cell Biodelivery™ device, NsG0202, capable of local delivery of NGF to the human cholinergic basal forebrain. Results from a small Phase 1b clinical study showed that the NGF dose could advantageously be increased. We have therefore developed a second generation clinical device named NsG0202.1, containing an RPE cell line (NGC0211) generated with transposon expression technology for highdose NGF production. Furthermore, to promote cell attachment and long-term viability of NGC0211, a polyethylene terephthalate (PET) yarn scaffolding was used. The safety was tested in Göttingen minipigs during a six months period with NsG0202.1 implants placed in the basal forebrain. The devices were well tolerated and the NGC0211 viability and NGF secretion remained after 6 months in vivo. The NGF induced relevant biological responses in the surrounding cholinergic target neurons.

Keywords:

Encapsulated Cell Biodelivery™, Gottingen minipigs, preclinical testing.