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Functional Validation of a New Therapeutic Strategy to Prevent Neurodegeneration and Subsequent Cognitive Impairment in Mouse Models of Alzheimer's Disease - NORLUX

Coordinating Institution: CRP Sante
Other Partner(s): Institut National Polytechnique de Lorraine (F)
From: 01/02/2007
To: 31/01/2009
Budget: 239,000.00€
Contact(s): Niclou Simone

Summary

Alzheimer’s disease is a neurodegenerative disease leading to progressive loss of memory and other bodily functions. This is due to the loss of neurons and of synaptic functions in response to aberrant proteins and peptides accumulating in the brain. Although the exact cause of the molecular and cellular changes are not understood, it is essential to develop strategies that can at least halt the ongoing neuronal loss. In this project we aimed to deliver a factor that can rescue dying neurons, in order to interfere with the progression of the disease. To this aim we have used small bioreactors that were implanted into the brain of mice and that are capable to provide longterm delivery of a therapeutic substance.

The bioreactor is based on living producer cells that are embedded (encapsulated) into a soft polymer and thus protected from destruction by the immune system. In this project we tested the hypothesis that this cell encapsulation technology could be used to deliver a neuroprotective factor into the brain of mice that show signs of Alzheimer’s disease. We choose a naturally occurring peptide called CNTF (Ciliary Neurotrophic Factor), that we had found to rescue cortical neurons from cell death induced by Alzheimer toxicity in vitro.

To test our hypothesis, the experiments were carried out in mice that, similar to patients, display cognitive (memory) defects and thus provide a relevant model for Alzheimer’s disease. The results of this work have been submitted for publication and are currently under revision. The present project will be extended in a new FNR project (CORE C08/BM/11) to expand the application of cell therapy based on alginate encapsulation to other brain disorders, including malignant brain tumors.

Refereed Scientific Publications:

CNTF cell based delivery prevents synaptic impairment and improves memory in mouse models of Alzheimer’s disease. P Garcia, I Youssef, JK Utvik, S Florent-Béchard, M Hanse, V Barthélémy, C Armand-Malaplate, B Kriem, C Stenger, V Koziel, JL Olivier, MC Escanye, A Allouche, C Desbène, FT Yen, R Bjerkvig, T Oster, SP Niclou and T Pillot (submitted).

N-truncated amyloid-beta oligomers induce learning impairment and neuronal apoptosis. Youssef I, Florent-Béchard S, Malaplate-Armand C, Koziel V, Bihain B, Olivier JL, Leininger-Muller B, Kriem B, Oster T, Pillot T. Neurobiol Aging. 2008 Sep;29(9):1319-33. Epub 2007 Apr 24.

Book chapters:

Treatment of brain tumors with micro-encapsulated cell therapy. Niclou SP & Bjerkvig R. Book chapter in: The Bioartificial Pancreas and other Biohybrid Therapies. 2009. Eds. Hallé, de Vos, Rosenberg. Transworld Research Network.

Treatment of Neurodegenerative Diseases (Parkinson's, Huntington's and Alzheimer's disease) with Cell Encapsulation Technology. Utvik JK & Niclou SP. Book chapter in: The Bioartificial Pancreas and other Biohybrid Therapies. 2009. Eds. Hallé, de Vos, Rosenberg. Transworld Research Network.