Grimpe, B: Role of the Extracellular Matrix in Axonal Regene

The suffering and tragedy associated with regeneration failure of the central nervous system (CNS) has spurred medical research for over a century. The extracellular matrix (ECM) assumes an essential function during such regeneration processes because it provides the surface for elongating axons and neuritis, stabilizes the synapses and confines further damage by forming the lesion scar. The development of easy to administer therapeutics in the treatment of acute spinal cord injury (SCI) is a long awaited intervention in the pursuit of finding a cure for paralysis. Therefore, this thesis summarizes investigations on ECM molecules such as nidogen-1, laminin gamma-1-chain, xylosyltransferase-1 (XT-1) and CD44osteopontin (OPN) interaction important during cell adhesion and regeneration processes. To respond to the pressing need of new therapeutics a knock down technology called deoxyribozymes or DNA enzymes were tested in various cell culture and animal experiments, which generated such potential drugs. Animals that received systemic administration of a DNA enzyme to XT-1 after a contusion injury of the thoracic spinal cord resulted in a significant improvement of sensorimotor function and increased serotonergic axon presence caudal to the injury, had no toxicological and pathological effects and neuropathic pain was not observed. Collectively, this demonstrates that the DNA enzyme technology generates safe neurotherapeutic, which hold promise to become an integral component of therapies that aim to improve the quality of life of persons with SCI.