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The challenges of regeneration failure in the central nervous system (CNS) have driven medical research for over a century. The extracellular matrix (ECM) plays a crucial role in these regeneration processes, providing surfaces for axon elongation, stabilizing synapses, and forming lesion scars to limit further damage. The quest for effective treatments for acute spinal cord injury (SCI) is ongoing, with a focus on developing easy-to-administer therapeutics to address paralysis. This thesis explores ECM molecules like nidogen-1, laminin gamma-1-chain, xylosyltransferase-1 (XT-1), and CD44-osteopontin (OPN), which are vital for cell adhesion and regeneration. To meet the urgent need for new therapies, a knockdown technology using deoxyribozymes or DNA enzymes was tested in various cell cultures and animal studies. Notably, animals receiving systemic administration of a DNA enzyme targeting XT-1 after thoracic spinal cord contusion showed significant improvements in sensorimotor function and increased serotonergic axon presence below the injury site, with no observed toxicological or pathological effects, nor neuropathic pain. This research highlights the potential of DNA enzyme technology as a safe neurotherapeutic, promising to enhance the quality of life for individuals with SCI.
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The role of the extracellular matrix in axonal regeneration and its treatment after spinal cord injury, Barbara Grimpe
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- Année de publication
- 2014
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