Encapsulated Cell Biodelivery of Nerve Growth Factor to the Basal Forebrain in Patients with Alzheimer’s Disease
| Autor: | Vesna Jelic, Kaj Blennow, Åke Seiger, Erik Sundström, Nenad Bogdanovic, Agneta Nordberg, Maria Kristoffersen Wiberg, Ahmadul Kadir, Per Almqvist, Maria Eriksdotter-Jönhagen, Niels Andreasen, Bengt Linderoth, Göran Lind, Layth Aladellie, Ove Almkvist, Lars Wahlberg, Lars-Olof Wahlund, Anders Wall, Bengt Winblad |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Nicotine Pathology medicine.medical_specialty Biopsy Cognitive Neuroscience Neuropsychological Tests Receptors Nicotinic Neurosurgical Procedures Cell Line Cognition Prosencephalon Alzheimer Disease medicine Humans Nerve Growth Factors Cholinergic neuron Cognitive decline Aged Aged 80 and over Cerebral Cortex Basal forebrain Dose-Response Relationship Drug Electroencephalography Infusion Pumps Implantable Middle Aged medicine.disease Magnetic Resonance Imaging Psychiatry and Mental health Treatment Outcome Nerve growth factor medicine.anatomical_structure nervous system Tolerability Cerebral cortex Positron-Emission Tomography Feasibility Studies Female Autopsy Implant Geriatrics and Gerontology Alzheimer's disease Psychology |
| Zdroj: | Dementia and Geriatric Cognitive Disorders. 33:18-28 |
| ISSN: | 1421-9824 1420-8008 |
| DOI: | 10.1159/000336051 |
| Popis: | Background/Aims: 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. Methods: 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. Results: 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. Conclusions: 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. |
| Databáze: | OpenAIRE |
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