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Vol. 33, No. 1, 2012
Issue release date: March 2012
Section title: Original Research Article
Dement Geriatr Cogn Disord 2012;33:18–28
(DOI:10.1159/000336051)

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

Eriksdotter-Jönhagen M. · Linderoth B. · Lind G. · Aladellie L. · Almkvist O. · Andreasen N. · Blennow K. · Bogdanovic N. · Jelic V. · Kadir A. · Nordberg A. · Sundström E. · Wahlund L.-O. · Wall A. · Wiberg M. · Winblad B. · Seiger Å. · Almqvist P. · Wahlberg L.
Departments of aNeurobiology, Caring Sciences and Society, bClinical Neuroscience and cClinical Science, Karolinska Institutet, Departments of dGeriatrics, eNeurosurgery, fEmergency Medicine and gRadiology, Karolinska University Hospital, hStockholms sjukhem, and iDepartment of Psychology, Stockholm University, Stockholm, jDepartment of Clinical Neuroscience, Clinical Neurochemistry Laboratory, University of Göteborg, Göteborg, and kDepartment of Radiology, Oncology and Radiation Sciences, Uppsala University, Uppsala, Sweden; lNsGene A/S, Ballerup, Denmark

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Article / Publication Details

First-Page Preview
Abstract of Original Research Article

Accepted: 12/20/2011
Published online: 2/22/2012

Number of Print Pages: 11
Number of Figures: 4
Number of Tables: 3

ISSN: 1420-8008 (Print)
eISSN: 1421-9824 (Online)

For additional information: http://www.karger.com/DEM

Abstract

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.


Article / Publication Details

First-Page Preview
Abstract of Original Research Article

Accepted: 12/20/2011
Published online: 2/22/2012

Number of Print Pages: 11
Number of Figures: 4
Number of Tables: 3

ISSN: 1420-8008 (Print)
eISSN: 1421-9824 (Online)

For additional information: http://www.karger.com/DEM


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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