GM1 gangliosidosis is a rare neurodegenerative lysosomal storage disease caused by loss-of-function mutations in the gene encoding beta-galactosidase (β-gal). There are no approved treatments for GM1 gangliosidosis. Previous studies in animal models have demonstrated that adeno-associated viral (AAV) vector-mediated gene transfer to the brain can restore β-gal expression and prevent the onset of neurological signs. We developed an optimized AAV vector expressing human β-gal and evaluated the efficacy of a single intracerebroventricular injection of this vector into the cerebrospinal fluid (CSF) of a murine disease model. The AAV vector administration into the CSF increased β-gal activity in the brain, reduced neuronal lysosomal storage lesions, prevented the onset of neurological signs and gait abnormalities, and increased survival. These findings demonstrate the potential therapeutic activity of this vector and support its subsequent development for the treatment of GM1 gangliosidosis.

中文翻译：

---

将优化的腺相关病毒载体单次注射到脑脊液中可纠正 GM1 神经节苷脂沉积症小鼠模型中的神经系统疾病

GM1 神经节苷脂贮积症是一种罕见的神经退行性溶酶体贮积病，由编码 β-半乳糖苷酶 (β-gal) 的基因功能丧失突变引起。GM1 神经节苷脂沉积症没有获批的治疗方法。先前在动物模型中的研究表明，腺相关病毒 (AAV) 载体介导的基因转移到大脑可以恢复 β-gal 表达并防止神经系统症状的发生。我们开发了一种表达人 β-gal 的优化 AAV 载体，并评估了将该载体单次脑室内注射到小鼠疾病模型的脑脊液 (CSF) 中的功效。将 AAV 载体给药到 CSF 中增加了大脑中的 β-gal 活性，减少了神经元溶酶体贮积病变，防止了神经系统体征和步态异常的发生，并提高了存活率。