Title:Lentiviral Micro-dystrophin Gene Treatment into Late-stage mdx Mice
for Duchenne Muscular Dystrophy Disease
Volume: 23
Issue: 4
关键词:
杜氏肌营养不良症，基因治疗，慢病毒，微肌营养不良蛋白基因，神经肌肉疾病，肌营养不良蛋白。
摘要:
Aim: Duchenne Muscular Dystrophy (DMD) results in a deficiency of dystrophin expression
in patient muscle fibers, leading to progressive muscle degeneration. Treatment of DMD has undertaken
current transformation with the advancement of novel gene therapy and molecular biology
techniques, which are secure, well-tolerated, and effective therapeutic approaches.
Introduction: DMD gene therapies have mainly focused on young DMD patients as in vivo animal
model trials have been performed in 0–1-month DMD mice. However, it has not yet been answered
how micro-dystrophin encoding lentiviral treatment affects Dystrophin expression and DMD symptoms
in 10-month mdx mice.
Methods: We planned to integrate the micro-Dystrophin gene sequence into the muscle cells by viral
transfer, using micro-Dystrophin-encoding lentivirus to reduce the dystrophic pathology in late-stage
dmd mice. The histopathological and physiological-functional regeneration activities of the lentiviralmicro-
Dystrophin gene therapy methods were compared, along with changes in temporal Dystrophin
expression and their functionality, toxicity, and gene expression level.
Results: Here, we showed that the micro-dystrophin transgene transfers intramuscularly and intraperitoneally
in late-stage dmd-mdx-4cv mice restored dystrophin expression in the skeletal and cardiac
muscle (p <0.001). Furthermore, motor performance analysis, including hanging and tracking tests,
improved statistically significantly after the treatment (p <0.05).
Conclusion: Consequently, this study suggests that patients in the late stages of muscular dystrophy
can benefit from lentiviral micro-dystrophin gene therapies to present an improvement in dystrophic
muscle pathology.
