在接受基因治疗后，芳香族L-氨基酸脱羧酶缺乏症（AADCd）患者在皮博迪发育运动量表第二版（PDMS-2）上出现了具有临床意义的改善，以及与贝利婴幼儿发展量表第三版（Bayley-III）评分和运动发育里程碑的相关性。
Clinically meaningful improvements after gene therapy for aromatic L-amino acid decarboxylase deficiency (AADCd) in the Peabody Developmental Motor Scale, Second Edition (PDMS-2) and correlation with Bayley-III scores and motor milestones.
作者信息
Hwu Wuh-Liang, Lee Hui-Min, Peipert John Devin, Zhang Rongrong, Werner Christian, Sierra J Rafael, O'Connell Thomas, Woolley Jonathan J, Crowell Marjorie, Wang Antonia, Tomazos Ioannis
机构信息
Department of Medical Genetics and Pediatrics, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
Centre for Patient Reported Outcomes Research, Department of Applied Health Sciences, University of Birmingham, Birmingham, UK.
出版信息
Orphanet J Rare Dis. 2025 Feb 7;20(1):58. doi: 10.1186/s13023-025-03584-9.
BACKGROUND
Aromatic L-amino acid decarboxylase deficiency (AADCd) is a rare genetic disorder characterized by movement disorders, motor and autonomic dysfunction, and developmental delays. The gene therapy eladocagene exuparvovec has become available in some regions; pooled clinical trial results demonstrate continuous long-term improvement in motor development and cognitive function. We sought to characterize clinically meaningful change in motor function, as measured by Total Peabody Developmental Motor Scales-Second Edition (PDMS-2) score, and assess correlations with cognition and language domains of the Bayley-III and motor milestone (MM) achievement.
METHODS
Data from N = 30 patients from three single-arm clinical studies of eladocagene exuparvovec were analyzed. Anchor-based estimation of the meaningful score difference (MSD) of Total PDMS-2 score was conducted using mean-difference and receiver operating characteristic curve (ROC) approaches. MM achievement served as the anchor defining meaningful change.
RESULTS
An MSD of 40 points for Total PDMS-2 score was selected for analysis as it yielded specificity > 0.95 using the ROC approach, and generally aligned with the mean-difference approach. Cumulative incidence analysis reflected that 50% of patients treated with eladocagene exuparvovec may achieve the MSD of 40-point change in Total PDMS-2 score at 6 months, and 86% at 18 months. Correlations between measures were of large magnitude and improved over time (Month 6: r = 0.599 [p = 0.0032]; Month 18: r = 0.796 [p = 0.0002]; Month 60: r = 0.861 [p = 0.0007]).
CONCLUSIONS
The MSD of 40 points for Total PDMS-2 score enables the interpretation of changes observed in patients with AADCd, and suggests that treatment with eladocagene exuparvovec leads to significant improvements in motor and cognitive function.
背景
芳香族L-氨基酸脱羧酶缺乏症（AADCd）是一种罕见的遗传性疾病，其特征为运动障碍、运动和自主神经功能障碍以及发育迟缓。基因疗法eladocagene exuparvovec已在一些地区可用；汇总的临床试验结果表明，运动发育和认知功能持续长期改善。我们试图通过总皮博迪发育运动量表第二版（PDMS-2）评分来描述运动功能的临床意义变化，并评估与贝利婴幼儿发展量表第三版（Bayley-III）的认知和语言领域以及运动里程碑（MM）达成情况的相关性。
方法
分析了来自eladocagene exuparvovec三项单臂临床研究的N = 30例患者的数据。使用均值差异和受试者工作特征曲线（ROC）方法对总PDMS-2评分的有意义评分差异（MSD）进行基于锚点的估计。MM达成情况作为定义有意义变化的锚点。
结果
总PDMS-2评分的MSD选择为40分进行分析，因为使用ROC方法时其特异性> 0.95，并且总体上与均值差异方法一致。累积发病率分析表明，接受eladocagene exuparvovec治疗的患者中有50%可能在6个月时实现总PDMS-2评分40分变化的MSD，18个月时为86%。各测量指标之间的相关性较大且随时间改善（第6个月：r = 0.599 [p = 0.0032]；第18个月：r = 0.796 [p = 0.0002]；第60个月：r = 0.861 [p = 0.0007]）。
结论
总PDMS-2评分40分的MSD有助于解释AADCd患者观察到的变化，并表明eladocagene exuparvovec治疗可显著改善运动和认知功能。
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