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OBJECT The authors describe the first clinical trial with encapsulated cell biodelivery (ECB) implants that deliver nerve growth factor (NGF) to the cholinergic basal forebrain with the intention of halting the degeneration of cholinergic neurons and the associated cognitive decline in patients with Alzheimer disease (AD). The NsG0202 implant (NsGene A/S)(More)
Nerve growth factor (NGF) is a potential therapeutic agent for Alzheimer's disease (AD) as it has positive effects on the basal forebrain cholinergic neurons whose degeneration correlates with the cognitive decline in AD. We have previously described an encapsulated cell biodelivery device, NsG0202, capable of local delivery of NGF by a genetically modified(More)
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(More)
Protein injection studies of the glial cell line derived neurotrophic factor (GDNF) family member Neurturin (NTN) have demonstrated neuroprotective effects on dopaminergic (DA) neurons, which are selectively lost during Parkinson's disease (PD). However, unlike GDNF, NTN has not previously been applied in PD models using an in vivo gene therapy approach.(More)
During the past decade, lentiviral vectors based on the HIV-1 genome have been developed to become highly useful tools for efficient and stable delivery of transgenes to dividing and nondividing cells in a variety of experimental protocols. The vector system has been progressively and substantially improved,mainly to meet growing concerns over safety(More)
BACKGROUND Gene therapy for neurodegenerative diseases depends critically on the vector system to direct sustained and stable expression of the transgene. It is, however, a commonly observed phenomenon that transgene expression from currently available vectors is down-regulated following ex vivo gene transfer to the central nervous system (CNS). In an(More)
Nerve Growth Factor (NGF) has therapeutic effects on the cholinergic neurodegeneration in Alzheimer’s disease (AD). We have previously described an implantable Encapsulated Cell BiodeliveryTM 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(More)
The development of a set of synthetic mammalian promoters with different specific activities is described. The library is based on a synthetic promoter, JeT, constructed as a 200 bp chimeric promoter built from fragments of the viral SV40 early promoter and the human beta-actin and ubiquitin C promoters. The JeT promoter was made by separating the included(More)
PURPOSE Encapsulated cell (EC) biodelivery is a promising, clinically relevant technology platform to safely target the delivery of therapeutic proteins to the central nervous system. The purpose of this study was to evaluate EC biodelivery of the novel neurotrophic factor, Meteorin, to the striatum of rats and to investigate its neuroprotective effects(More)
BACKGROUND Deep brain stimulation (DBS) in experimental animals has promoted new indications and refined existing treatments. Implantation of downscaled clinical DBS leads directly compatible with commercially available implantable pulse generators can however be challenging. Accordingly, we have developed a lead implantation device (LID) and technique for(More)