Neurodegenerative Studies Laboratory

Patrick Aebischer, MD.
Professor

Link: http://len.epfl.ch

Research Interests

Neurodegenerative diseases represent an heterogeneous group of disorders that usually strike in mid-life, causing progressive loss of motor and cognitive function. Although clinical manifestations vary, the outcome is the same: patients become incapacitated over a period of years and finally die. Tackling neurodegenerative diseases thus represents a formidable challenge for our ageing society.

A first axis of our research focuses on the development of rodent animal models to improve our understanding of the molecular basis of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD). Concomitantly, we are developing gene therapy strategies aimed at correcting gene defects or treating its consequences. Both overexpression for loss of functions and gene silencing through RNAi techniques are being investigated. To that purpose, we are using two distinct gene therapy approaches to deliver candidate genes in animal models of the diseases: (i) the direct in vivo lentiviral and AAV vector delivery (in vivo gene therapy); and (ii) the encapsulation of genetically engineered cell lines releasing the therapeutic molecules (ex vivo gene therapy).

The functional effects are characterized through the use of a wide variety of techniques including behavioural assessment, in vivo imaging techniques, morphological analysis and biochemical measurements.

Our laboratory consists in approximately 800 m2 of a start-of-the art facility including tissue culture rooms of P2 levels, dedicated sections for molecular biology, biochemistry, immunohistochemistry, morphology, imaging analysis and virus production (Lentivirus and AAV). Central facilities include a cell sorter facility, 2-photons and confocal equipment and an animal care SPF facility including a P2 and P3 area with respective behavioural rooms. Expertise in each of these techniques is assured by specifically trained collaborators.

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Key Publications

• J. Szulc, M. Wiznerowicz, D. Trono, P. Aebischer Versatile tool for conditional gene expression and knockdown Nature Methods, 3 : 109-116, 2006


• C. Raoul, T. Abbas-Terkik, J.C. Bensadoun, S. Guillot, J. Szulc, G. Haas, C. Henderson, P. Aebischer Lentiviral-mediated silencing of SOD-1 through RNA interference retards onset and progression in a mouse model of ALS Nature Medicine, 11: 423-428, 2005


• C. Lo Bianco, B. L. Schneider, M. Bauer, A. Sajidi, A. Brice, T. Iwatsubo, P. Aebischer Lentiviral delivery of parkin prevents dopaminergic degeneration in an a-synuclein rat model of Parkinson's disease PNAS, 101: 17150-17155, 2004


• A. Sajadi, B.L. Schneider, P. Aebischer WLDs-mediated protection of dopaminergic fibers in an animal model of Parkinson disease Current in Biology, 14 : 326-330, 2004


• C. Lo Bianco, J-L- Ridet, B. Schneider, N. Déglon, P. Aebischer Lentiviral-mediated overepression of a-synuclein in the rat susbtantia nigra as a genetic model for Parkinson's disease PNAS, 99: 10813-10818, 2002


• Kordower, J.H., Emborg, M.E., Bloch, J., Ma, S.Y., Chu, Y., Leventhal, L., McBride, J., Chen, E., Palfi, S., Roitberg, B., Brown, W.D., Holden, J.E., Pyzalski, R., Taylor, M.D., Carvey, P., Ling, Z., Trono, D., Hantraye, P., Déglon, N., and Aebischer, P. Neurodegeneration Prevented by Lentiviral Vector Delivery of GDNF in Primate Models of Parkinson's Disease. Science 290: 767-773, 2000