A154: MyoAAV 2a-Mediated Neurturin Improves the Pathological and MotorFunction of Mdx Mice

<bold>Background/Purpose:</bold> Neurturin is a muscle secretory factor mediated by PGC-1Α1. Studies have shown that Neurturin has the function of coordinating the integrity of muscle fibers and their motor neurons and improving motor ability. Duchenne muscular dystrophy is a neuromuscular disease in which people gradually lose their mobility. Therefore, the aim of this study was to explore the pathological improvement of mdx mice treated with Neurturin. <bold>Methods:</bold> (1) MyoAAV 2A-Neurturin viral tool was prepared by HEK293T three-plasmid system. (2) Three male and three female SPF newborn C57BL/10ScSn mice and six male and six female C57BL/10scsn-Dmd<italic>mdx</italic>/J mice were used in the experiment. C57 mice were used as the control group (C57+PBS), and mdx mice were divided into virus injection group (<italic>mdx</italic>+Ntrn) and control group (<italic>mdx</italic>+PBS). The mice in the <italic>mdx</italic>+Ntrn were injected with 1.0E+13 vg/kg MyoAAV 2A-Neurturin, and the mice in the C57+PBS and <italic>mdx</italic>+Ntrn were injected with the same volume of PBS. (3) Grip strength, treadmill running performance, and creatine kinase were measured after 4 weeks. (4) Statistical methods: The results were expressed as mean ± standard error, a one-way ANCOVA test was used between groups, and <italic>P</italic> &lt; 0.05 was considered statistically significant. <bold>Results:</bold> (1) The titer of MyoAAV 2A-Neurturin was 1.0E+13 vg/ml. The migration distance of VP1:VP2:VP3 bands in silver staining was consistent with that of the corresponding molecular weight bands in Marker, and the ratio was close to 1:1:10. (2) In the grip strength test, compared with the <italic>mdx</italic>+PBS, the relative grip strength of the <italic>mdx</italic>+Ntrn increased (<italic>P</italic> = 0.022). Compared with the C57+PBS, relative grip strength of the <italic>mdx</italic>+Ntrn increased, but the difference was not statistically significant (<italic>P</italic> = 0.122). (3) In the treadmill running performance test, compared with the <italic>mdx</italic>+PBS, the exhaustion time of the <italic>mdx</italic>+Ntrn significantly increased (<italic>P</italic> &lt; 0.05). (4) Compared with the <italic>mdx</italic>+PBS, the CK level of the mdx+Ntrn significantly decreased (<italic>P</italic> &lt; 0.05). The CK level of the <italic>mdx</italic>+Ntrn showed a downward trend, but the difference was not statistically significant (<italic>P</italic> = 0.099). <bold>Conclusion/Discussion:</bold> The grip strength and exhaustion time of <italic>mdx</italic> mice were improved, and the level of creatine kinase decreased. Neurturin improved the pathological and motor function of <italic>mdx</italic> mice. This study provided a new attempt for the application of Neurturin in mdx mice and provides a new idea for the treatment of Duchenne muscular dystrophy.