BackgroundSpinocerebellar ataxia type 3 (SCA3) is an autosomal dominant inherited neurodegenerative disorder for which there is currently no cure, nor effective treatment strategy.ObjectiveOur aim was to investigate the safety and efficacy of high‐dose ganglioside GM1 (ganglioside‐monosialic acid) pulse treatment in patients with SCA3.MethodsPatients 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.ResultsA 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.ConclusionsHigh‐dose GM1 treatment significantly ameliorated ataxic symptoms in patients with SCA3. © 2024 International Parkinson and Movement Disorder Society.

中文翻译：

---

神经节苷脂 GM1 脉冲治疗对 3 型脊髓小脑性共济失调的潜在疾病缓解作用，一项平行组、双盲、随机、对照试验


背景脊髓小脑性共济失调 3 型 （SCA3） 是一种常染色体显性遗传性神经退行性疾病，目前尚无治愈方法，也没有有效的治疗策略。目的我们的目的是探讨大剂量神经节苷脂 GM1 （神经节苷脂-单唾液酸） 冲击治疗 SCA3 患者的安全性和有效性。方法患者被随机分配接受高剂量 GM1 （第一天 400 mg，然后 200 mg/天）、低剂量 GM1 （40 mg/天） 或安慰剂 （生理盐水） 4 周。通过测量共济失调评估和评级量表 （SARA） 评分从基线到治疗后 12 周的变化来评估主要结果，是评估治疗效果的核心。次要结局包括国际合作共济失调评定量表 （ICARS） 评分、Barthel 日常生活活动指数 （ADL） 以及血浆和脑脊液 （CSF） GABA 水平的变化。对所有接受治疗的患者进行了安全性评估。结果本研究共纳入 48 例 SCA3 患者。12 周后，来自 43 例患者的数据被纳入疗效分析 （意向性治疗分析）。高剂量 GM1 组 SARA 评分从基线到治疗后 12 周的最小二乘平均变化为 -3.80（标准误差 [SE]，0.39;95% 置信区间 [CI]，-4.58 至 -3.02），低剂量 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）。 分别。次要结局显示，与低剂量 GM1 和安慰剂组相比，高剂量 GM1 组的 ICARS 评分、ADL 的 Barthel 指数以及血浆和 CSF GABA 水平有所改善。所有治疗均具有良好的耐受性和安全性。结论大剂量 GM1 治疗显著改善了 SCA3 患者的共济失调症状。© 2024 年国际帕金森和运动障碍协会。