Glial cell line-derived neurotrophic factor: a novel trophic factor in the meso-striatal system

Growth factors play an important role in the central nervous system, because they regulate the survival and growth of different cells in the brain. The aim of this project was to study the role of the growth factor "glial-cell-line- derived neurotrophic factor, GDNF" in the brain. Our experiments were performed in different models, like e.g. malignant glioma cells, primary neurons or glia and the organotypic brain slice model. Especially the brain slice model is very interesting, because this 3-dimensional model allows to study different cells in close connection. For this model, Prof. Humpel has received the "Staatspreis for Alternatives in Animal Research (2000)". The experiments clearly showed that GDNF is an important factor, which regulates the survival of dopamine releasing neurons. These neurons degenerate in Parkinsons disease, thus GDNF may be an important candidate in a therapeutic treatment. For the work on GDNF Prof. Humpel received the "NOVARTIS-Award for medicine, 1997" and the "W. BIRKMAYER-Award 1998" of the Austrian Parkinson Society. The studies also showed that GDNF has a potent effect on the proliferation of cells in brain tumors; this was shown in cell culture using C6 glioma cells but also in human patients tissue. Thus knock out of GDNF may be an interesting therapeutic approach in treating brain tumors. In further experiments we were interested to study gene therapeutic approaches. Especially lipid-mediated gene transfer is of interest and we could prepare genetically modified neurons and glia, cells which could be used for e.g. transplantation studies. Using this method we could also introduce short single stranded DNA molecules (oligonucleotides) into the cells and could knock out GDNF in these cells and subsequently inhibit proliferation. This approach may become an interesting therapeutic strategy in treating brain tumors. For this work Prof. Humpel has received the "PFIZER CNS Research Award 2000". Taken together, growth factors are interesting molecules for treating neurodegenerative disorders of the brain, such as e.g. GDNF in treating Parkinsons disease or NGF in treating Alzheimers disease. For these studies Prof. Humpel has recently received the "OTTO-LOEWI" Award 2001 of the Austrian Neuroscience Association. Zusammenfassend sind Wachstumsfaktoren interessante Moleküle, die bei degenerativen Erkrankungen des Gehirns eingesetzt werden können, wie z.B. GDNF bei Parkinson oder NGF bei Alzheimer. Für diese Arbeiten wurde Prof. Humpel kürzlich der "OTTO-LOEWI" Award 2001 der Austrian Neuroscience Association überreicht.