Novel strategies for spinal cord repair

脊髓修复的新策略

• 批准号: 423242406
• 负责人: Professor Dr. Dietmar Fischer
• 金额: --
• 依托单位: Zentrum für Pharmakologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/423242406?language=en
• 关键词: Novel; strategies; spinal; cord; repair

Axons in the central nervous system (CNS) of adult mammals do not normally regenerate and their damage usually leads to irreparable dysfunctions and severe disabilities. The applicant’s lab was able to show that the continuous release of hyper-interleukin-6 (hIL-6) from transduced retinal ganglion cells by postinjury application of adeno-associated virus (AAV) provides one of the strongest regenerative effects in the optic nerve achieved so far. The first objective of the proposed research project is therefore to test the hypothesis that a similar approach can be successfully applied to other CNS areas as well, such as the injured spinal cord and lead to functional recovery. A second goal is the investigationwhether parthenolide, which promotes peripheral nerve regeneration and improves hIL-6-induced optic nerve regeneration, can either alone or in combination with hIL-6 treatment also enhance axon regeneration in the spinal cord. For this purpose, di-methyl-amino-parthenolide (DMAPT) a water-soluble prodrug of parthenolide will be administered systemically. It is expected that this proposal will lead to new, potentially translatable approaches to improve functional recovery after spinal cord injury.

成年哺乳动物中枢神经系统（CNS）中的轴突通常不会再生，它们的损伤通常会导致不可修复的功能障碍和严重残疾。申请人的实验室能够表明，通过损伤后应用腺相关病毒（AAV）从转导的视网膜神经节细胞连续释放超白细胞介素-6（hIL-6）提供了迄今为止在视神经中实现的最强的再生效果之一。因此，拟议的研究项目的第一个目标是测试一个假设，即类似的方法也可以成功地应用于其他中枢神经系统领域，如受损的脊髓，并导致功能恢复。第二个目标是研究促进周围神经再生和改善hIL-6诱导的视神经再生的孤雌激素单独或与hIL-6联合治疗是否也能促进脊髓轴突再生。为此目的，将全身施用二甲基氨基-小白菊素（DMAPT），一种小白菊素的水溶性前药。预计这一建议将导致新的，潜在的翻译方法，以改善脊髓损伤后的功能恢复。