PD Dr. Barbara Grimpe
Each year approximately 100,000 individuals worldwide endure a spinal cord injury (SCI). In spite of centuries of research no satisfying treatment is available for this disease. This is mainly due to complex systems behavior, which makes it difficult for scientists to comprehend the entire processes. My group has set its dedication to develop new therapeutics via the utilization of a knock down technology called deoxyribozyme to reduce proteins, which are inhibitory to axonal growth. To identify these suitable molecules, so called “key player” my laboratory has additionally developed a prototypic computer program suite. This program provides an overall picture of SCI, its underlying biochemical pathways, potential protein interactions and lays hand on the sheer number of applied substances. Together these two approaches hold promise to find a treatment for paralysis.
The translational work in my laboratory utilizes the clinical relevant contusion injury model to mimic 70% of spinal cord injuries that occur in humans.
Novel Therapeutics: Deoxyribozymes are single-stranded catalytic DNA molecules of approximately 35 bases, which bind to a target mRNA via their sequence specific binding-arms and act as enzymes via a catalytic loop. The digested fragments are released and the deoxyribozyme is able to cleave further mRNA molecules of the same gene. Due to their easy administration, reliability, specificity, and low production costs deoxyribozymes will be an integral part of future therapies to improve the quality of life of persons with SCI.
Systems biology: In today’s scientific world we are overwhelmed with data. Concealed in this data is potentially useful information that is rarely made explicit. As part of systems biology, data/text mining and natural language processing search for patterns and hidden correlation in data. Together they pursue the simulation of complex biological systems utilizing diverse experimental sources. Hence, the application to real world problems (applied systems biology) provides solutions to untreatable diseases such as SCI.
In modern medicine both approaches will be beneficial to mankind.
1. Grimpe B. (2012) Deoxyribozymes and Bioinformatics: Complementary tools to investigate axon regeneration. Cell and Tissue Research, 349(1): 181-200 PubMed
2. Grimpe B. (2011) Deoxyribozymes: New therapeutics to treat central nervous system disorders. Frontiers in Neuroscience, 4: 25 PubMed
3.Hurtado A., Podini H., Oudega M., Grimpe B (2008) Deoxyribozyme-mediated knock down of xylosyltransferase-1 mRNA promotes sensory axon regeneration in the adult rat spinal cord. Brain, 131: 2596-605 PubMed
4. Ries A., Goldberg JL, Grimpe B. (2007) A novel biological function for CD44 and osteopontin in axon growth of retinal ganglion cells identified by a bioinformatics approach. Journal of Neurochemistry, 103: 1491-1505 PubMed
5. Grimpe B., Pressman Y., Lupa M.D., Horn K.P., Bunge M.B., Silver J. (2005) The role of proteoglycans in Schwann cell/astrocyte interactions and in regeneration failure at PNS/CNS interfaces. Molecular and Cellular Neuroscience 28: 18-29 PubMed
6. Grimpe B., Silver J. (2004) A novel DNA-enzyme reduces glycosaminoglycan chains in the glial scar and allows microtransplanted DRG axons to regenerate beyond lesions in the spinal cord. Journal of Neuroscience 24: 1393-1397 PubMed
7. Grimpe B. (2004) Aspects of antisense oligodeoxynucleotide, ribozyme, DNA enzyme and RNAi design. Current Medicinal Chemistry-Central Nervous System Agents 4: 1-15. Bentham Science
8. Grimpe B., Dong S., Doller C., Temple K., Malouf A.T., Silver J. (2002), The critical role of basement membrane independent laminin gamma 1 chain during axon regeneration in the CNS. Journal of Neuroscience 22: 3144-3160 PubMed
9. Grimpe B., Silver J (2002) The extracelluar matrix in axon regeneration. Prog Brain Res 137: 333-349. PubMed
10. Grimpe B., Probst J.C., Hager G. (1999) Suppression of nidogen-1 translation by antisense targeting affects the adhesive properties of cultured astrocytes. Glia 28: 138-149 PubMed