Evidence map›Paper›PMID 27389402›Full record

ArticleAlzheimer's research & therapy2016

Targeted delivery of nerve growth factor to the cholinergic basal forebrain of Alzheimer's disease patients: application of a second-generation encapsulated cell biodelivery device.

Helga Eyjolfsdottir, Maria Eriksdotter, Bengt Linderoth, Göran Lind, Bengt Juliusson, Philip Kusk, Ove Almkvist, Niels Andreasen, Kaj Blennow, Daniel Ferreira and 14 more

Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's research & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01163825 (An Open Label, Dose-Escalation Study of Encapsulated Cell Biodelivery of Nerve Growth Factor to the Cholinergic Basal Forebrain of Alzheimer´s Disease Patients), which is not on this map. Cited by 70 papers.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed
8.4field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01163825 phase1unknown statusnot on this map

An Open Label, Dose-Escalation Study of Encapsulated Cell Biodelivery of Nerve Growth Factor to the Cholinergic Basal Forebrain of Alzheimer´s Disease Patients

TypeinterventionalSponsorNsGene A/SRan2008Enrolled6ConditionsAlzheimer's DiseaseArmsNerve Growth Factor
3 · Its place in the literature

Who cites it

70 citing papers in PubMed, 143 citations in OpenAlex.

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  8. Targeted gene delivery systems for T-cell engineering.Cellular oncology (Dordrecht, Netherlands) · 2024
    Review
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  10. Polyethersulfone Polymer for Biomedical Applications and Biotechnology.International journal of molecular sciences · 2024
    Review
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10 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors at 5 institutions in 2 countries.

Helga EyjolfsdottirDepartment of Neurobiology, Care Sciences and Society, Karolinska Institutet, 171 77, Stockholm, Sweden.
Maria EriksdotterDepartment of Neurobiology, Care Sciences and Society, Karolinska Institutet, 171 77, Stockholm, Sweden.
Bengt LinderothDepartment of Clinical Neuroscience, Karolinska Institutet, 171 77, Stockholm, Sweden.
Göran LindDepartment of Clinical Neuroscience, Karolinska Institutet, 171 77, Stockholm, Sweden.
Bengt JuliussonNsGene Inc., 225 Chapman Street, Providence, RI, 02905-4533, USA.
Philip KuskNsGene Inc., 225 Chapman Street, Providence, RI, 02905-4533, USA.
Ove AlmkvistDepartment of Neurobiology, Care Sciences and Society, Karolinska Institutet, 171 77, Stockholm, Sweden.
Niels AndreasenDepartment of Neurobiology, Care Sciences and Society, Karolinska Institutet, 171 77, Stockholm, Sweden.
Kaj BlennowClinical Neurochemistry Laboratory, Department of Clinical Neuroscience, University of Gothenburg, 41345, Gothenburg, Sweden.
Daniel FerreiraDepartment of Neurobiology, Care Sciences and Society, Karolinska Institutet, 171 77, Stockholm, Sweden.
Eric WestmanDepartment of Neurobiology, Care Sciences and Society, Karolinska Institutet, 171 77, Stockholm, Sweden.
Inger NennesmoDepartment of Laboratory Medicine, Section of Pathology, Karolinska University Hospital, 171 76, Stockholm, Sweden.
Azadeh KaramiDepartment of Neurobiology, Care Sciences and Society, Karolinska Institutet, 171 77, Stockholm, Sweden.
Taher Darreh-ShoriDepartment of Neurobiology, Care Sciences and Society, Karolinska Institutet, 171 77, Stockholm, Sweden.
Ahmadul KadirDepartment of Neurobiology, Care Sciences and Society, Karolinska Institutet, 171 77, Stockholm, Sweden.
Agneta NordbergDepartment of Neurobiology, Care Sciences and Society, Karolinska Institutet, 171 77, Stockholm, Sweden.
Erik SundströmDepartment of Neurobiology, Care Sciences and Society, Karolinska Institutet, 171 77, Stockholm, Sweden.
Lars-Olof WahlundDepartment of Neurobiology, Care Sciences and Society, Karolinska Institutet, 171 77, Stockholm, Sweden.
Anders WallDepartment of Surgical Sciences, Section of Nuclear Medicine and PET, Uppsala University Hospital, 75185, Uppsala, Sweden.
Maria WibergDepartment of Clinical Science, Intervention and Technology, Division of Medical Imaging and Technology, Karolinska Institutet, 171 77, Stockholm, Sweden.
Bengt WinbladDepartment of Neurobiology, Care Sciences and Society, Karolinska Institutet, 171 77, Stockholm, Sweden.
Åke SeigerDepartment of Neurobiology, Care Sciences and Society, Karolinska Institutet, 171 77, Stockholm, Sweden.
Lars WahlbergDepartment of Neurobiology, Care Sciences and Society, Karolinska Institutet, 171 77, Stockholm, Sweden.
Per AlmqvistDepartment of Clinical Neuroscience, Karolinska Institutet, 171 77, Stockholm, Sweden. per.almqvist@ki.se.ORCID 0000-0002-0383-8189
Karolinska University Hospital · SEKarolinska Institutet · SEProvidence College · USUniversity of Gothenburg · SEUppsala University Hospital · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTargeted delivery of nerve growth factor (NGF) has emerged as a potential therapy for Alzheimer's disease (AD) due to its regenerative effects on basal forebrain cholinergic neurons. This hypothesis has been tested in patients with AD using encapsulated cell biodelivery of NGF (NGF-ECB) in a first-in-human study. We report our results from a third-dose cohort of patients receiving second-generation NGF-ECB implants with improved NGF secretion.

methodsFour patients with mild to moderate AD were recruited to participate in an open-label, phase Ib dose escalation study with a 6-month duration. Each patient underwent stereotactic implant surgery with four NGF-ECB implants targeted at the cholinergic basal forebrain. The NGF secretion of the second-generation implants was improved by using the Sleeping Beauty transposon gene expression technology and an improved three-dimensional internal scaffolding, resulting in production of about 10 ng NGF/device/day.

resultsAll patients underwent successful implant procedures without complications, and all patients completed the study, including implant removal after 6 months. Upon removal, 13 of 16 implants released NGF, 8 implants released NGF at the same rate or higher than before the implant procedure, and 3 implants failed to release detectable amounts of NGF. Of 16 adverse events, none was NGF-, or implant-related. Changes from baseline values of cholinergic markers in cerebrospinal fluid (CSF) correlated with cortical nicotinic receptor expression and Mini Mental State Examination score. Levels of neurofilament light chain (NFL) protein increased in CSF after NGF-ECB implant, while glial fibrillary acidic protein (GFAP) remained stable.

conclusionsThe data derived from this patient cohort demonstrate the safety and tolerability of sustained NGF release by a second-generation NGF-ECB implant to the basal forebrain, with uneventful surgical implant and removal of NGF-ECB implants in a new dosing cohort of four patients with AD.

trial registrationClinicalTrials.gov identifier: NCT01163825 . Registered on 14 Jul 2010.

Indexed as

Drug Delivery SystemsAcetylcholinesteraseAgedAlzheimer DiseaseAmyloid beta-PeptidesBasal ForebrainCapsulesCell LineCholine O-AcetyltransferaseCognition DisordersCohort StudiesDose-Response Relationship, DrugFemaleHumansMaleMiddle AgedAcetylcholinesteraseAmyloid beta-Peptidesamyloid beta-protein (1-42)CapsulesCholine O-AcetyltransferaseNerve Growth FactorNerve Tissue ProteinsNGF protein, humanPeptide Fragmentstau ProteinsAlzheimer’s diseaseEncapsulated cell biodeliveryNerve growth factorRegenerative medicine

Identifiers

PMID27389402
PMCPMC4936020
OpenAlexW2469782527

What OpenQuestion holds

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LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.