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J Alzheimers Dis. 2015;43(3):1059-72. doi: 10.3233/JAD-141068.

Brain changes in Alzheimer's disease patients with implanted encapsulated cells releasing nerve growth factor.

Author information

1
Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
2
Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden Department of Geriatrics, Karolinska University Hospital, Stockholm, Sweden.
3
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden.
4
Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden Department of Geriatrics, Karolinska University Hospital, Stockholm, Sweden Stockholms Sjukhem, Stockholm, Sweden.
5
Department of Clinical Neuroscience, Clinical Neurochemistry Laboratory, University of Göteborg, Mölndal Campus, Sweden.
6
Department of Clinical Science, Intervention and Technology, Division of Medical Imaging and Technology, Karolinska Institutet, Stockholm, Sweden Department of Radiology, Karolinska University Hospital, Stockholm, Sweden.
7
Department of Neuroimaging, Institute of Psychiatry, King's College London, London, UK.
8
NsGene Inc., Rhode Island, USA.

Abstract

New therapies with disease-modifying effects are urgently needed for treating Alzheimer's disease (AD). Nerve growth factor (NGF) protein has demonstrated regenerative and neuroprotective effects on basal forebrain cholinergic neurons in animal studies. In addition, AD patients treated with NGF have previously shown improved cognition, EEG activity, nicotinic binding, and glucose metabolism. However, no study to date has analyzed brain atrophy in patients treated with NGF producing cells. In this study we present MRI results of the first clinical trial in patients with AD using encapsulated NGF biodelivery to the basal forebrain. Six AD patients received the treatment during twelve months. Patients were grouped as responders and non-responders according to their twelve-months change in MMSE. Normative values were created from 131 AD patients from ADNI, selecting 36 age- and MMSE-matched patients for interpreting the longitudinal changes in MMSE and brain atrophy. Results at baseline indicated that responders showed better clinical status and less pathological levels of cerebrospinal fluid (CSF) Aβ1-42. However, they showed more brain atrophy, and neuronal degeneration as evidenced by higher CSF levels of T-tau and neurofilaments. At follow-up, responders showed less brain shrinkage and better progression in the clinical variables and CSF biomarkers. Noteworthy, two responders showed less brain shrinkage than the normative ADNI group. These results together with previous evidence supports the idea that encapsulated biodelivery of NGF might have the potential to become a new treatment strategy for AD with both symptomatic and disease-modifying effects.

KEYWORDS:

ADNI; Alzheimer's disease; brain changes; cerebrospinal fluid biomarkers; clinical progression; clinical trial; encapsulated cell biodelivery; nerve growth factor; neurofilaments; structural MRI

PMID:
25147108
DOI:
10.3233/JAD-141068
[Indexed for MEDLINE]

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