In vitro and in vivo gene therapy with CMV vector-mediated presumed dog nerve growth factor in pyridoxine-induced neuropathy dogs Download

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Due to the therapeutic potential of gene therapy for neuronal injury, many studies of neurotrophic factors, vectors, and animal models have been performed. The presumed dog nerve growth factor (pd¥â-NGF) was generated and cloned and its expression was confirmed in CHO cells. The recombinant NGF protein reacted with a human NGF antibody and showed bioactivity in PC12 cells. The NGF was shown to have similar bioactivity to the dog NGF. The recombinant NGF plasmid was administrated into the intrathecal space in the gene therapy group. Twenty-four hours after the vector inoculation, the gene therapy group and the positive control group were intoxicated with excess pyridoxine for seven days. Each morning throughout the test period, the dogs body weight was taken and postural reaction assessments were made. Electrophysiological recordings were performed twice, once before the experiment and once after the test period. After the experimental period, histological analysis was performed. Dogs in the gene therapy group had no weight change and were normal in postural reaction assessments. Electrophysiological recordings were also normal for the gene therapy group. Histological analysis showed that neither the axons nor the myelin of the dorsal funiculus of L4 were severely damaged in the gene therapy group. In addition, the dorsal root ganglia of L4 and the peripheral nerves (sciatic nerve) did not experience severe degenerative changes in the gene therapy group. This study is the first to show the protective effect of NGF gene therapy in a dog model.

Submitted On:

08 Jan 2009

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File Date:

08 Jan 2009

File Author:

Jin-Young Chung, Jung-Hoon Choi, Il-Seob Shin, Eun-Wha Choi, Cheol-Yong Hwang, Sang-Koo Lee, Hwa-You

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