Population, Policy and Practice Programme, UCL Great Ormond Street Institute of Child Health, London, WC1N 1EH, UK.
Department of Pharmacology, University of Oxford, Oxford, OX1 3QT, UK.
Orphanet J Rare Dis. 2018 Aug 16;13(1):143. doi: 10.1186/s13023-018-0880-9.
Niemann-Pick disease type C (NPC) is a lysosomal storage disease with a heterogeneous neurodegenerative clinical course. Multiple therapies are in clinical trials and inclusion criteria are currently mainly based on age and neurological signs, not taking into consideration differential individual rates of disease progression.
In this study, we have evaluated a simple metric, denoted annual severity increment score (ASIS), that measures rate of disease progression and could easily be used in clinical practice. We show that ASIS is stable over several years and can be used to stratify patients for clinical trials. It achieves greater homogeneity of the study cohort relative to age-based inclusion and provides an evidence-based approach for establishing inclusion/exclusion criteria. In addition, we show that ASIS has prognostic value and demonstrate that treatment with an experimental therapy - acetyl-DL-leucine - is associated with a reduction in ASIS scores.
ASIS has the potential to be a useful metric for clinical monitoring, trial recruitment, for prognosis and measuring response to therapy.
尼曼-匹克病 C 型（NPC）是一种溶酶体贮积病，具有异质性神经退行性临床过程。多种疗法正在临床试验中，目前纳入标准主要基于年龄和神经体征，而没有考虑到疾病进展的个体差异率。
在这项研究中，我们评估了一种简单的指标，称为年度严重程度递增评分（ASIS），用于衡量疾病进展速度，可在临床实践中轻松使用。我们表明，ASIS 多年来保持稳定，可用于对患者进行临床试验分层。与基于年龄的纳入标准相比，它使研究队列更加同质，并为建立纳入/排除标准提供了基于证据的方法。此外，我们表明 ASIS 具有预后价值，并证明实验性治疗——乙酰-DL-亮氨酸——与 ASIS 评分降低相关。
ASIS 有可能成为一种有用的临床监测、试验招募、预后和治疗反应测量指标。
