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Targeted delivery o...
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
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- Eyjolfsdottir, H. (författare)
- Karolinska Institutet
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- Eriksdotter, M. (författare)
- Karolinska Institutet
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- Linderoth, B. (författare)
- Karolinska Institutet
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- Lind, G. (författare)
- Karolinska Institutet
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- Juliusson, B. (författare)
- NsGene Inc, 225 Chapman St, Providence, RI 02905 USA.
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- Kusk, P. (författare)
- NsGene Inc, 225 Chapman St, Providence, RI 02905 USA.
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- Almkvist, O. (författare)
- Karolinska Institutet
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- Andreasen, N. (författare)
- Karolinska Institutet
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- Blennow, Kaj, 1958 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology,Univ Gothenburg, Dept Clin Neurosci, Clin Neurochem Lab, S-41345 Gothenburg, Sweden.
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- Ferreira, D. (författare)
- Karolinska Institutet
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- Westman, E. (författare)
- Karolinska Institutet
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- Nennesmo, I. (författare)
- Karolinska Institutet
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- Karami, A. (författare)
- Karolinska Institutet
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- Darreh-Shori, T. (författare)
- Karolinska Institutet
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- Kadir, A. (författare)
- Karolinska Inst, Dept Neurobiol Care Sci & Soc, S-17177 Stockholm, Sweden.
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- Nordberg, A. (författare)
- Karolinska Inst, Dept Neurobiol Care Sci & Soc, S-17177 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Geriatr, S-17176 Stockholm, Sweden.
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- Sundstrom, E. (författare)
- Karolinska Institutet
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- Wahlund, L. O. (författare)
- Karolinska Institutet
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- Wall, Anders (författare)
- Uppsala universitet,Radiologi
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- Wiberg, M. (författare)
- Karolinska Institutet
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- Winblad, B. (författare)
- Karolinska Institutet
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- Seiger, A. (författare)
- Karolinska Institutet
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- Wahlberg, L. (författare)
- Karolinska Inst, Dept Neurobiol Care Sci & Soc, S-17177 Stockholm, Sweden.;NsGene Inc, 225 Chapman St, Providence, RI 02905 USA.
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- Almqvist, P. (författare)
- Karolinska Institutet
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Karolinska Institutet NsGene Inc, 225 Chapman St, Providence, RI 02905 USA (creator_code:org_t)
- 2016-07-07
- 2016
- Engelska.
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Ingår i: Alzheimers Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 8
- Relaterad länk:
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https://alzres.biome...
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https://uu.diva-port... (primary) (Raw object)
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Background: Targeted 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. Methods: Four 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. Results: All 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. Conclusions: The 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Nyckelord
- Nerve growth factor
- Alzheimer's disease
- Regenerative medicine
- Encapsulated cell biodelivery
- neurodegenerative diseases
- cerebrospinal-fluid
- sleeping-beauty
- brain
- ngf
- gene
- csf
- therapy
- protein
- technology
- Nerve growth factor
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Eyjolfsdottir, H ...
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Eriksdotter, M.
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Linderoth, B.
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Lind, G.
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Juliusson, B.
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Kusk, P.
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visa fler...
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Almkvist, O.
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Andreasen, N.
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Blennow, Kaj, 19 ...
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Ferreira, D.
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Westman, E.
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Nennesmo, I.
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Karami, A.
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Darreh-Shori, T.
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Kadir, A.
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Nordberg, A.
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Sundstrom, E.
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Wahlund, L. O.
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Wall, Anders
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Wiberg, M.
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Winblad, B.
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Seiger, A.
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Wahlberg, L.
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Almqvist, P.
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Neurologi
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Alzheimers Resea ...
- Av lärosätet
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Göteborgs universitet
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Uppsala universitet
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Karolinska Institutet