Novel strategies for spinal cord repair

成年哺乳动物的中枢神经系统(CNS)中的轴突通常不会再生，它们的损伤通常会导致无法修复的功能障碍和严重的残疾。申请人的实验室能够证明，通过在腺相关病毒(AAV)的作用下，转导的视网膜神经节细胞持续释放高白介素6(hIL-6)，在视神经中提供了迄今所取得的最强的再生效应之一。因此，拟议研究项目的第一个目标是检验这样一个假设，即类似的方法也可以成功地应用于其他中枢神经系统区域，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巴特内酯是否可以单独或与hIL-6联合治疗也促进脊髓轴突再生。为此，将系统地给药二甲氨基菊酯(DMAPT)，这是一种菊内酯的水溶性前药。预计这项建议将导致新的，潜在的可翻译的方法，以改善脊髓损伤后的功能恢复。

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.