n -乙酰的有效性和安全性l-儿童和成人GM2神经节糖苷剂量的亮氨酸JF神经学JO神经学FD Lippincott Williams & Wilk半岛投注体育官网ins SP e1072 OP e1083 DO 10.1212/WNL.0000000000201660VO 100 IS 10 A1 Martakis, Kyriakos A1 Claassen, Jens A1 Gascon-Bayari, Jordi A1 Goldschagg, Nicolina A1 Hahn, Andreas A1 Hassan, Anhar A1 Hennig, Anita A1 Jones, Simon A1 Kay, Richard A1 Lau, Heather A1 Perlman, Susan A1 Sharma, Reena A1 Schneider, Susanne A1 Bremova-Ertl, Tatiana YR 2023 UL http://n.半岛投注体育官网neurology.org/content/100/10/e1072.abstract神经退行性疾病，没有有效的对症治疗或疾病缓解治疗。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