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Encapsulated Cell Biodelivery of Nerve Growth Factor to the Basal Forebrain in Patients with Alzheimer’s Disease

2012; Karger Publishers; Volume: 33; Issue: 1 Linguagem: Inglês

10.1159/000336051

1421-9824

Maria Eriksdotter, Bengt Linderoth, Göran Lind, Layth Aladellie, Ove Almkvist, Niels Andreasen, Kaj Blennow, Nenad Bogdanović, Vesna Jelić, Ahmadul Kadir, Agneta Nordberg, Erik Sundström, Lars‐Olof Wahlund, Anders Wall, Maria Kristoffersen Wiberg, Bengt Winblad, Åke Seiger, Per Almqvist, Lars U. Wahlberg,

Neurogenesis and neuroplasticity mechanisms

<i>Background/Aims:</i> Degeneration of cholinergic neurons in the basal forebrain correlates with cognitive decline in patients with Alzheimer’s disease (AD). Targeted delivery of exogenous nerve growth factor (NGF) has emerged as a potential AD therapy due to its regenerative effects on the basal forebrain cholinergic neurons in AD animal models. Here we report the results of a first-in-man study of encapsulated cell (EC) biodelivery of NGF to the basal forebrain of AD patients with the primary objective to explore safety and tolerability. <i>Methods:</i> This was an open-label, 12-month study in 6 AD patients. Patients were implanted stereotactically with EC-NGF biodelivery devices targeting the basal forebrain. Patients were monitored with respect to safety, tolerability, disease progression and implant functionality. <i>Results:</i> All patients were implanted successfully with bilateral single or double implants without complications or signs of toxicity. No adverse events were related to NGF or the device. All patients completed the study, including removal of implants at 12 months. Positive findings in cognition, EEG and nicotinic receptor binding in 2 of 6 patients were detected. <i>Conclusions:</i> This study demonstrates that surgical implantation and removal of EC-NGF biodelivery to the basal forebrain in AD patients is safe, well tolerated and feasible.