Klinische Forschergruppe Neuroregeneration
Josef-Schneider-Str. 11, 97080 Würzburg
Other participating persons and organisations:
Research foci (and basic equipment-based research projects):
In motoneuron disorders, the pathogenesis is not yet elucidated and effective treatments are not existing. The identification of gene defects in patients with spinal muscular atrophy (SMA) and familial types of amyotrophic lateral sclerosis (fALS) points to a reverse cellular basis of motoneuron degeneration. Some of the recently identified genes play a role in intracellular signaling relevant for cell survival. The molecular characterization of neurotrophic factors and the analysis of effects of these factors on motoneuron survival opens new strategies for clinical and basic research. If it were possible to elucidate the role of neurotrophic factors in signal transaction and the interactions with pathways relevant for cell death and apoptosis this would be potentially leading to new therapies. The work of this research group is largely based on mouse models and on clinical and experimental pilot trials with neurothrophic factors studying mechanisms of application, bio availability toxicity and therapeutic efficacy.
During 1997-2000, a series of papers were published in the area of neuronal survival and neurite outgrowth. We could show, that adenoviral gene transfer of CNTF and BDNF prevents degeneration of motoneuron cell bodies, even after prolonged periods of 5 weeks. We could also show, that glutamate signalling specifically modulates dendrite growth of cultured motoneurons, and that p75 neurotrophin receptor signalling is necessary for mediating survival signals in lesioned postnatal motoneurons. A series of animal models were generated, in particular in the areas of spinal muscular atrophy and neurotrophin signalling. The Klinische Forschergruppe was also involved in phase I/II studies with ALS patients, which received BDNF intra-thecally in order to test tolerability and efficacy of this neurotrophic factor.
Results from the Klinische Forschergruppe during 1997-2000 were published in more than 20 papers in Nature Neuroscience, Nature Cell Biology, Nature Medicine, Journal of Neuroscience and PNAS. During the same time, 9 book chapters and reviews were published from this research group.
Rewards and prizes:
1994 Wilhelm Vaillant-Preis der Wilhelm Vaillant-Stiftung
1997 ALS-Forschungspreis der Deutschen Gesellschaft für Muskelkranke
Laboratories for the Klinische Forschergruppe für Neuroregeneration were part of the Department of Neurology University of Würzburg. There were 3 laboratories (S 1), 1 laboratory for viral gene transfer (S 2), 2 cell culture labs and laboratories for generation of transgenic mice. Moreover, 1 office room and 1 additional lab for scientific instruments was available to the Forschergruppe.
The Forschergruppe also had access to central facilities for radioactive research. The Klinische Forschergruppe Neuroregeneration has played a central role in the planning of reconstruction and renovation of animal facilities which are located besides the Kopfklinikum.
The Deutsche Forschungsgemeinschaft has provided several microscopes, including a confocal microscope and microscopes for blastocyste injection, HPLC. The Free State of Bavaria has provided additional grants for centrifuges, laboratory instruments and other equipment.
An autoclave for the animal facility was provided by the Free State of Bavaria and the German Government in 1998. Additional grants from the Klinikum of the University of Würzburg were used for buying a phospho-imager. This instrument is also available to other research groups located in the Department of Neurology and other clinical departments in the Kopfklinikum.