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Document Type

Abstract

Publication Date

12-1-2024

Abstract

Background/Purpose: 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.

Methods: (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-Dmdmdx/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 (mdx+Ntrn) and control group (mdx+PBS). The mice in the mdx+Ntrn were injected with 1.0E+13 vg/kg MyoAAV 2A-Neurturin, and the mice in the C57+PBS and mdx+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 P < 0.05 was considered statistically significant.

Results: (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 mdx+PBS, the relative grip strength of the mdx+Ntrn increased (P = 0.022). Compared with the C57+PBS, relative grip strength of the mdx+Ntrn increased, but the difference was not statistically significant (P = 0.122). (3) In the treadmill running performance test, compared with the mdx+PBS, the exhaustion time of the mdx+Ntrn significantly increased (P < 0.05). (4) Compared with the mdx+PBS, the CK level of the mdx+Ntrn significantly decreased (P < 0.05). The CK level of the mdx+Ntrn showed a downward trend, but the difference was not statistically significant (P = 0.099).

Conclusion/Discussion: The grip strength and exhaustion time of mdx mice were improved, and the level of creatine kinase decreased. Neurturin improved the pathological and motor function of mdx 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.

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