Chen Yong-Kang, Tian Hai-Yan, Zhu Qing-Yong, Zhang Rui, Liang Dong-Xiao, Wang Jiu-Qi, Feng Ren-Yi, Qin Chi, Ma Ming-Ming, Jiang Hong, Tang Bei-Sha, Ding Xue-Bing, Wang Xue-Jing
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Henan Key Laboratory of Chronic Disease Prevention and Therapy & Intelligent Health Management, Zhengzhou, China.
Mov Disord. 2025 Jan;40(1):57-66. doi: 10.1002/mds.30050. Epub 2024 Nov 7.
Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant inherited neurodegenerative disorder for which there is currently no cure, nor effective treatment strategy.
Our aim was to investigate the safety and efficacy of high-dose ganglioside GM1 (ganglioside-monosialic acid) pulse treatment in patients with SCA3.
Patients were randomly allocated to receive either high-dose GM1 (400 mg on the first day followed by 200 mg/day), low-dose GM1 (40 mg/day), or placebo (normal saline) for 4 weeks. The primary outcome, assessed by measuring the change in the Scale for the Assessment and Rating of Ataxia (SARA) scores from baseline to 12 weeks post-treatment, is central to evaluating treatment efficacy. Secondary outcomes included changes in the International Cooperative Ataxia Rating Scale (ICARS) score, Barthel Index of Activities of Daily Living (ADL), and plasma and cerebrospinal fluid (CSF) GABA levels. Safety was assessed in all treated patients.
A total of 48 patients with SCA3 were enrolled in this study. After 12 weeks, data from 43 patients were included in the efficacy analysis (intention-to-treat analysis). The least-squares mean change in the SARA score from baseline to 12 weeks post-treatment was -3.80 (standard error [SE], 0.39; 95% confidence interval [CI], -4.58 to -3.02) in the high-dose GM1 group, 0.34 (SE, 0.40; 95% CI, -0.46 to 1.13) in the low-dose GM1 group, and 0.73 (SE, 0.40; 95% CI, -0.07 to 1.52) in the placebo group, respectively. Secondary outcomes showed improvements in the ICARS score, Barthel Index of ADL, and plasma and CSF GABA levels in the high-dose GM1 group compared to the low-dose GM1 and placebo groups. All treatments were well-tolerated and safe.
High-dose GM1 treatment significantly ameliorated ataxic symptoms in patients with SCA3. © 2024 International Parkinson and Movement Disorder Society.
3型脊髓小脑共济失调（SCA3）是一种常染色体显性遗传的神经退行性疾病，目前尚无治愈方法，也没有有效的治疗策略。
我们的目的是研究大剂量神经节苷脂GM1（单唾液酸神经节苷脂）脉冲治疗SCA3患者的安全性和疗效。
将患者随机分配，分别接受大剂量GM1（第1天400mg，随后每天200mg）、小剂量GM1（每天40mg）或安慰剂（生理盐水）治疗4周。通过测量共济失调评估和评分量表（SARA）从基线到治疗后12周的评分变化来评估的主要结局，对于评估治疗效果至关重要。次要结局包括国际合作共济失调评分量表（ICARS）评分、日常生活活动巴氏指数（ADL）以及血浆和脑脊液（CSF）γ-氨基丁酸水平的变化。对所有接受治疗的患者进行安全性评估。
本研究共纳入48例SCA3患者。12周后，43例患者的数据纳入疗效分析（意向性分析）。大剂量GM1组从基线到治疗后12周SARA评分的最小二乘均值变化为-3.80（标准误[SE]，0.39；95%置信区间[CI]，-4.58至-3.02），小剂量GM1组为0.34（SE，0.40；95%CI，-0.46至1.13），安慰剂组为0.73（SE，0.40；95%CI，-0.07至1.52）。次要结局显示，与小剂量GM1组和安慰剂组相比，大剂量GM1组的ICARS评分、ADL巴氏指数以及血浆和脑脊液γ-氨基丁酸水平有所改善。所有治疗耐受性良好且安全。
大剂量GM1治疗可显著改善SCA3患者的共济失调症状。©2024国际帕金森病和运动障碍协会。
