Novel strategies for spinal cord repair

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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.