Reconstruction of Impaired CNS Pathway using Adenovirus Vector

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It has been widely believed the mammalian CNS does not regenerate. But our laboratory demonstrated that marked regeneration is possible under the favorable condition. The condition mainly depends on the formation of glial scar. We have set up the hypothesis that tumor suppressor gene trasfer using adenovirus vector into the CNS traumatic lesion would inhibit the subsequent formation of gliosis and lead to induction of marked axonal regenaration. We selected NBS1 as candidate, which is reported to be mutated or deleted in Nijmegen breakage syndrome, presenting B-cell lymphoma with a high incidence.In contrary to our expect, our data did not showed correlation between NBS1 and malignant lymphoma.We tested the adenovirus vector as a tool for gene delivery, using Wistar strain rat. Two to 28 days after the adenovirus injection into the local spinal cord, the distribution of lacZ was examined. It was detected not only in injection site (spinal cord) but also in choroid plexus, basal ganglia, dura etc. There was no pareplegic or fatal animal. Thus we confirmed the usefulness an d safety of adenoviurus as a deliver of gene in the treatment of CNS injury.This study elucidates the therapeutic breakthrough in the spinal cord injury, cerebral apoplexy, and CNS degenerative disease if appropriate gene candidate is obtained.