TY - JOUR T1 - n -乙酰-l- leucine在儿童和成人GM2神经节糖苷剂量中的疗效和安全性JF -神经学JO -神经学SP - e1072 LP - e1083 DO - 10.1212/WNL.0半岛投注体育官网000000000201660六世- 100 - 10盟Martakis Kyriakos盟——Claassen Jens AU - Gascon-Bayari乔迪盟——Goldschagg Nicolina AU -哈恩,安德烈亚斯AU -哈桑,安哈AU -亨尼希,安妮塔非盟-琼斯,理查德•刘盟——西蒙•凯盟-希瑟AU -珀尔曼苏珊盟,沙玛,丽娜AU -施耐德,Susanne盟——Bremova-Ertl Tatiana Y1 - 2023/03/07 UR - //www.ebmtp.com/content/100/10/e1072.abstract N2 -背景和目标GM2 gangliosidoses(家族黑蒙性白痴和Sandhoff疾病)是罕见的,半岛投注体育官网常染色体隐性遗传，神经退行性疾病，没有可用的对症或疾病修饰治疗。这项临床试验研究了n -乙酰-l-亮氨酸(NALL)，一种口服的修饰氨基酸，用于GM2神经节苷化剂量的儿童(≥6岁)和成人患者。方法:在IIb期多国、开放标签、分级盲法研究(ib101 -202)中，基因诊断为GM2神经节苷酸剂量的≥6岁的男性和女性患者接受口服NALL 6周治疗期(≥13岁患者4 g/d, 6- 12岁患者按体重分级给药)，随后是6周的治疗后洗脱期。对于严重程度变化的主要临床印象分析，患者在预定的主要锚试验(8米行走试验或9孔钉试验)中的表现在基线时，在NALL试验6周后，在6周洗脱期后再次被录像并由盲评分者集中评估。次要结果包括评估共济失调、临床整体印象和生活质量。结果入选患者30例，年龄6 ~ 55岁。29例患者进行了治疗评估，并纳入了主要的改良意向治疗分析。该研究达到了其CI- cs主要终点(平均差0.71,SD = 2.09, 90% CI 0.00, 1.50, p = 0.039)，以及共济失调和整体印象的次要指标。NALL安全、耐受性好，无严重不良反应。Discussion Treatment with NALL was associated with statistically significant and clinically relevant changes in functioning and quality of life in patients with GM2 gangliosidosis. NALL was safe and well tolerated, contributing to an overall favorable risk:benefit profile. NALL is a promising, easily administered (oral) therapeutic option for these rare, debilitating diseases with immense unmet medical needs.Trial Registration Information The trial is registered with ClinicalTrials.gov (NCT03759665; registered on November 30, 2018), EudraCT (2018-004406-25), and DRKS (DRKS00017539). The first patient was enrolled on June 7, 2019.Classification of Evidence This study provides Class IV evidence that NALL improves outcomes for patients with GM2 gangliosidoses.8MWT=8-Meter Walk Test; AE=adverse event; CGI=Clinical Global Impression; MCL=Medpace Core Laboratories; NPC=Niemann-Pick disease type C; SARA=Scale for the Assessment and Rating of Ataxia; SCAFI=Spinocerebellar Ataxia Functional Index; SAP=statistical analysis plan; TEAE=treatment-emergent adverse event; VAS=visual analog scale ER -