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期刊来源：Nat Med

原文链接：https://doi.org/10.1038/s41591-024-02886-y

摘要内容如下：

Prasinezumab是一种结合聚集的α-突触核蛋白的单克隆抗体，目前正在研究将其作为早期帕金森病的潜在疾病改善疗法。尽管在帕萨迪纳2期研究中，未达到主要终点（运动障碍学会统一帕金森病评定量表（MDS-UPDRS）第I+II+III部分的总和），但接受普拉西珠单抗治疗的个体的运动体征进展比安慰剂治疗的参与者慢（MDS-UPDRS第III部分）。我们在此报告了一项探索性分析，评估在预先指定的运动进展较快的亚组中，普拉西珠单抗是否对运动体征进展显示出更大的益处。在帕萨迪纳的四个预先指定的和六个探索性亚群中评估了普拉西珠单抗对疾病进展的潜在影响：基线时使用单胺氧化酶B抑制剂（是与否）；Hoehn和Yahr阶段（2对1）；快速眼动睡眠行为障碍（有与无）；数据驱动的亚表型（弥漫性恶性与非弥漫性恶性）；基线年龄（≥60岁对<60岁）；性别（男性对女性）；疾病持续时间（>12个月对<12个月）；诊断时的年龄（≥60岁对<60岁）；运动亚表型（运动不能-僵硬对震颤-显性）；和运动亚表型（姿势不稳、步态功能障碍与震颤为主）。在这些亚群中，普拉西珠单抗对减缓运动体征进展（MDS-UPDRS第三部分）的作用在快速进展的亚群（例如，弥漫性恶性或基线时服用单胺氧化酶B抑制剂的参与者）中更大。这项探索性分析表明，在为期1年的试验中，普拉西珠单抗可能在更大程度上减少进展更快的帕金森病患者的运动进展。然而，由于这是一项事后分析，需要额外的随机临床试验来验证这些发现。

英文原文如下：

Abstracts

Prasinezumab, a monoclonal antibody that binds aggregated α-synuclein, is being investigated as a potential disease-modifying therapy in early-stage Parkinson's disease. Although in the PASADENA phase 2 study, the primary endpoint (Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) sum of Parts I + II + III) was not met, prasinezumab-treated individuals exhibited slower progression of motor signs than placebo-treated participants (MDS-UPDRS Part III). We report here an exploratory analysis assessing whether prasinezumab showed greater benefits on motor signs progression in prespecified subgroups with faster motor progression. Prasinezumab's potential effects on disease progression were assessed in four prespecified and six exploratory subpopulations of PASADENA: use of monoamine oxidase B inhibitors at baseline (yes versus no); Hoehn and Yahr stage (2 versus 1); rapid eye movement sleep behavior disorder (yes versus no); data-driven subphenotypes (diffuse malignant versus nondiffuse malignant); age at baseline (≥60 years versus <60 years); sex (male versus female); disease duration (>12 months versus <12 months); age at diagnosis (≥60 years versus <60 years); motor subphenotypes (akinetic-rigid versus tremor-dominant); and motor subphenotypes (postural instability gait dysfunction versus tremor-dominant). In these subpopulations, the effect of prasinezumab on slowing motor signs progression (MDS-UPDRS Part III) was greater in the rapidly progressing subpopulations (for example, participants who were diffuse malignant or taking monoamine oxidase B inhibitors at baseline). This exploratory analysis suggests that, in a trial of 1-year duration, prasinezumab might reduce motor progression to a greater extent in individuals with more rapidly progressing Parkinson's disease. However, because this was a post hoc analysis, additional randomized clinical trials are needed to validate these findings.

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