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

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 high- dose 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 Gottingen 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.