A new step towards using stem cells to treat Parkinson's disease

Research by a team at the Institut Pasteur associated with the CNRS published today in Nature Neuroscience is uncoveringsignificant prospects for developing cell therapies to repair the brain. These researchers have succeeded in triggering the transformation of neuronal stem cells from the adult brains of mice into neurons capable of secreting dopamine, a molecule lacking in Parkinson's disease.

 

 

Press release
Paris, june 13, 2005

 

 

Parkinson’s is due to the degeneration of neurons producing dopamine in the brain. This extremely debilitating disease affects nearly four million people throughout the world and its incidence is on the rise in industrialised nations as life expectancy improves. Recently, the discovery of the existence of stem cells in the adult brain has raised new hopes in developing cell therapies. Pierre-Marie Lledo’s team at the Institut Pasteur (Perception and Memory Unit, CNRS URA 2182) demonstrated that the adult brain produces neoneurons capable of establishing new connections there (1), and then, one year later, that these neoneurons can be guided towards precise regions of the brain (2). In order to apply these discoveries to treating brain injuries or diseases, they still had to ensure that the neoneurons recruited in this way would actually produce dopamine, the molecule that produces the repairs required for treating Parkinson’s.

Researchers from Lledo’s team, in collaboration with Magdalena Götz’s team from the University of Munich (Germany), have recently shown that they were able to provoke the differentiation of neuronal precursors in mice into dopamine neurons. They succeeded in directing the maturation of the majority of neoneurons, which came from a precise area of the brain, into neurons producing and secreting dopamine. To do this, they used viral vectors inducing the production of an activating molecule, a transcription factor called Pax6, in the neuronal stem cells and neuronal precursors. Their experiments were followed in the olfactory bulb, one of the few brain tissues where the recruitment of new neurons can be observed in adults.

"Our work could contribute to elaborating new therapeutic strategies that make it possible to choose the cellular destiny of newly-formed neurons, then to divert them from their germ layer to the regions to be repaired", Lledo commented.

These results open up considerable prospects for treating neurodegenerative diseases, combining a gene therapy approach (orienting the evolution of stem cells) with cell therapy (leading these cells towards a specific area of the brain). The researchers are now going to test the feasibility of such therapies on animal models of Parkinson’s.

Sources

" Neuronal fate determinants of adult olfactory bulb neurogenesis" Nat. Neurosci. Juin 2005.
Michael Hack (1), Armen Saghatelyan (2), Antoine de Chevigny (2), Alexander Pfeifer (1), Ruth Ashery-Padan (1) Pierre-Marie Lledo (2) & Magdalena Götz (1).

1. GSF – National Research Center for Environment and Health, Institute for Stem Cell Research, Ingolstädter Landstraße 1, D-85764 Neuherberg/Munich, Germany
2. Unité postulante de Perception et Mémoire Olfactive, CNRS URA 2182, Institut Pasteur

(1) " Becoming a new neuron in the adult forebrain" Nat. Neurosci. 6, 507-518 (2002) .
Alan Carleton (1), Leopoldo T. Petreanu (2), Rusty Lansford (3), Arturo Alvarez-Buylla (4) & Pierre-Marie Lledo (1)

1. Unité postulante de Perception et Mémoire Olfactive, CNRS URA 2182, Institut Pasteur
2. The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
3. Division of Biology, Biological Imaging Center, Beckman Institute, California Institute of Technology, Pasadena, California 91125, USA
4. Neurosurgery Research, UCSF, San Francisco, California 94134, USA

(2) "Tenascine-R mediates activity dependent recruitment of neuroblasts in the adult mouseforebrain" Nat. Neurosci. 7, 347-356 (2003 .
Armen Saghatelyan (1), Antoine de Chevigny (1), Melitta Schachner (2) & Pierre-Marie Lledo (1)

1. Unité postulante de Perception et Mémoire Olfactive, CNRS URA 2182, Institut Pasteur
2. Zentrum für Molekulare Neurobiologie, Universität Hamburg, Martinistrasse 52, D-20246 Hamburg, Germany

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