Shapiro Barbara E, Pastores Gregory M, Gianutsos John, Luzy Cécile, Kolodny Edwin H
Department of Neurology, University Hospitals Case Medical Center, Cleveland, Ohio 44106-5098, USA.
Genet Med. 2009 Jun;11(6):425-33. doi: 10.1097/GIM.0b013e3181a1b5c5.
To evaluate the safety and efficacy of miglustat in patients with GM2 gangliosidosis.
A randomized, multicenter, open-label, 12-month study involving patients aged 18 years or older, randomized 2:1 to miglustat (200 mg TID) or "no miglustat treatment." This study was followed by 24 months of extended treatment during which all patients received miglustat. Primary efficacy endpoints were change in eight measures of isometric muscle strength in the limbs and isometric grip strength, evaluated at baseline, and months 12 and 36. Secondary efficacy endpoints included gait, balance, disability, and other neurological assessments. Safety evaluations included adverse event reporting.
Thirty patients (67% male, age range 18-56 years) with late-onset Tay-Sachs disease were enrolled; 20 were randomized to miglustat and 10 to "no miglustat treatment." Muscle and grip strength generally decreased over the study period. No differences were observed between the two groups in any efficacy measure, either during the 12-month randomized phase or the full 36 months. The most common treatment-related adverse events were decrease in weight and diarrhea.
Miglustat treatment was not shown to lead to measurable benefits in this cohort of patients with late-onset Tay-Sachs disease. The observed safety profile was consistent with that of the approved dose (100 mg TID) in type 1 Gaucher disease.
评估米格鲁司他对GM2神经节苷脂贮积症患者的安全性和有效性。
一项随机、多中心、开放标签的12个月研究，纳入18岁及以上患者，按2:1随机分为米格鲁司他组（200毫克，每日三次）或“无米格鲁司他治疗”组。该研究之后是24个月的延长治疗期，在此期间所有患者均接受米格鲁司他治疗。主要疗效终点为基线、第12个月和第36个月时四肢等长肌肉力量的八项指标及等长握力的变化。次要疗效终点包括步态、平衡、残疾及其他神经学评估。安全性评估包括不良事件报告。
纳入30例晚发性泰-萨克斯病患者（67%为男性，年龄范围18 - 56岁）；20例随机分配至米格鲁司他组，10例分配至“无米格鲁司他治疗”组。在研究期间，肌肉力量和握力总体上有所下降。在12个月的随机阶段或整个36个月期间，两组在任何疗效指标上均未观察到差异。最常见的与治疗相关的不良事件是体重减轻和腹泻。
在这组晚发性泰-萨克斯病患者中，未显示米格鲁司他治疗有可测量的益处。观察到的安全性特征与1型戈谢病中批准剂量（100毫克，每日三次）的安全性特征一致。
