Preclinical assessment of therapeutic strategies in models of Amyotrophic Lateral Sclerosis and Parkinson Disease

Team Leader

Dr. Bettina Göricke & Dr. Tobias Frank

phone:
+ 49 - 551 - 39 14343
fax:
+ 49 - 551 - 39 14302
e-mail:
tobias.frank(at)med.uni-goettingen.de, bgoericke(at)med.uni-goettingen.de
Abstract

We focus on therapeutic strategies with translational potential for fast application in human patients. Examples are repositioning of drugs, which are already in clinical use. In general we are testing promising molecules in a preclinical animal setting. We are interested in both efficiency and pharmacokinetic data collection.

We make use of molecular analysis, imaging techniques and animal models.

Moreover, we participate in the ambulant care of patients suffering from neurodegenerative disorders (Parkinson syndromes, Motor neuron diseases). Here, we are involved in networks with close contact to innovative diagnostic and therapeutic strategies (MND-Net). We participate in multicenter clinical therapeutic studies and are also interested in development of new diagnostic tools like real-time MRI and Biomarker-CSF studies.

Tools & Models
  • MPTP mouse model, 6 OHDA rat model, ALS mouse and rat model (SOD1G93A)
  • CSF collection from rats, HPLC from mouse striata
  • Cell culture (primary-, cell lines), ELISA, Western Blot, qPCR, cloning techniques
  • Immunohistochemistry, -cytochemistry

The Team

Dr. Tobias Frank

Placeholder
phone:
+ 49 - 551 - 39 14343
fax:
+ 49 - 551 - 39 14302
e-mail:
tobias.frank(at)med.uni-goettingen.de
Main Research Interest

After proof of principle that granulocyte colony-stimulating factor (G-CSF) exerts neuroprotective effects in rodent Parkinson models, we evaluated a pharmacological improved version with longer half life and superior properties compared to non-modified G-CSF. However, the optimal dose and injection interval is still under investigation.

Dosing of G-CSF might also be influenced on its influence on neuogenesis which is another focus of our work.

We also participated in a collaboration testing new small antiaggregative molecules in Parkinson disease and other “aggregopathies”. In the future therapeutic strategies might be driven into combination of such treatments with neurotrophin application like G-CSF.

Current Projects
  • Optimal dosing and injection interval of pegylated G-CSF to exert neuroprotective effects in rodent Parkinson models
  • Effect of G-CSF on dopaminergic neurogenesis
  • Antiinflammatory treatment strategies in models of Parkinson disease
  • Evaluation of interactions between cytokines and alpha-synuclein
Publications
  1. 1. Lars Tönges*, Tobias Frank*, et al. Inhibition of Rho Kinase enhances survival of dopaminergic neurons and preserves axonal loss in a mouse model of Parkinson’s disease, Brain, 2012, accepted for publishing (* shared first authorship)
  2. 2. Dupuis, L., et al., A Randomized, Double Blind, Placebo-Controlled Trial of Pioglitazone in Combination with Riluzole in Amyotrophic Lateral Sclerosis. PLoS One, 2012. 7(6): p. e37885. (Co-Authorship for the GERP ALS Study Group)
  3. 3. Jens Wagner, et al., Anle138b: A novel oligomer modulator for the treatment of prion and Parkinson´s disease, Science Translational Medicine, 2012, in Revision (Co-Authorship)
  4. 4. T. Frank, F. Klinker, D. Liebetanz, K. Meuer, W.J. Schulz-Schaeffer, J.B. Schulz, A. Schneider, M. Bähr, J.H. Weishaupt. Pegylated Granulocyte-Colony-Stimulating Factor (G-CSF) prevents dopaminergic cell loss in models of Parkinson´s Disease. Brain 2012; doi: 10.1093/brain/aws054
  5. 5. T. Frank, J.C.M Schlachetzki, B. Göricke, K. Meuer, G. Rohde, G.P.H. Dietz, M. Bähr, A. Schneider, J.H. Weishaupt. Both systemic and local application of Granulocyte-Colony Stimulating Factor (G-CSF) is neuroprotective after retinal ganglion cell axotomy. BMC Neuroscience 2009. 2009 May 14;10:49

 

Dr. Bettina Göricke

Placeholder
phone:
+ 49 - 551 - 39 14343
fax:
+ 49 - 551 - 39 14302
e-mail:
bgoericke(at)med.uni-goettingen.de
Publications
  1. Tobias Frank et al. Pegylated granulocyte colony-stimulating factor conveys long-term neuroprotection and improves functional outcome in a model of Parkinson's disease. Brain 2012; doi: 10.1093/brain/aws054.
  2. Göricke, B., et al. Cerebellar-type multiple system atrophy presenting with leucoencephalopathy. J Neurol Neurosurg Psychiatry (2010).
  3. T. Frank, et. al. Both systemic and local application of Granulocyte-Colony Stimulating Factor (G-CSF) is neuroprotective after retinal ganglion cell axotomy. BMC Neurosci. 2009 May 14;10:49.
  4. Meuer, K., et al. Cyclin-dependent kinase 5 is an upstream regulator of mitochondrial fission during neuronal apoptosis. Cell Death Differ 14, 651-661 (2007).
  5. Meuer, K., et al. Granulocyte-colony stimulating factor is neuroprotective in a model of Parkinson's disease. J Neurochem 97, 675-686 (2006).
  6. Cantz, T., et al. Quantitative gene expression analysis reveals transition of fetal liver progenitor cells to mature hepatocytes after transplantation in uPA/RAG-2 mice. Am J Pathol 162, 37-45 (2003).

Sabine Ceramella, TA

phone:
+49 - 551 - 39 14304
e-mail:
sceramella(at)web.de
Sabine Ceramella, TA

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