Sivananthan Siyamini, Lee Laura, Anderson Glenn, Csanyi Barbara, Williams Ruth, Gissen Paul
Department of Inherited Metabolic Diseases, Great Ormond Street Hospital, London WC1N 1EH, UK.
Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre, University College London, London WC1N 1EH, UK.
Brain Sci. 2023 Jan 27;13(2):209. doi: 10.3390/brainsci13020209.
The introduction of intracerebroventricular (ICV) enzyme replacement therapy (ERT) for treatment of neuronal ceroid lipofuscinosis type 2 (CLN2) disease has produced dramatic improvements in disease management. However, assessments of therapeutic effect for ICV ERT are limited to clinical observational measures, namely the CLN2 Clinical Rating Scale, a subjective measure of motor and language performance. There is a need for an objective biomarker to enable assessments of disease progression and response to treatment. To address this, we investigated whether the proportion of cells with abnormal storage inclusions on electron microscopic examination of peripheral blood buffy coats could act as a biomarker of disease activity in CLN2 disease. We conducted a prospective longitudinal analysis of six patients receiving ICV ERT. We demonstrated a substantial and continuing reduction in the proportion of abnormal cells over the course of treatment, whereas symptomatic scores revealed little or no change over time. Here, we proposed the use of the proportion of cells with abnormal storage as a biomarker of response to therapy in CLN2. In the future, as more tissue-specific biomarkers are developed, the buffy coats may form part of a panel of biomarkers in order to give a more holistic view of a complex disease.
脑室内（ICV）酶替代疗法（ERT）用于治疗2型神经元蜡样脂褐质沉积病（CLN2），在疾病管理方面取得了显著进展。然而，对ICV ERT治疗效果的评估仅限于临床观察指标，即CLN2临床评分量表，这是一种对运动和语言表现的主观测量方法。需要一种客观的生物标志物来评估疾病进展和对治疗的反应。为了解决这一问题，我们研究了在外周血血沉棕黄层的电子显微镜检查中，具有异常储存包涵体的细胞比例是否可作为CLN2疾病活动的生物标志物。我们对6名接受ICV ERT的患者进行了前瞻性纵向分析。我们证明，在治疗过程中，异常细胞的比例大幅且持续下降，而症状评分随时间几乎没有变化。在此，我们提出将具有异常储存的细胞比例用作CLN2治疗反应的生物标志物。未来，随着更多组织特异性生物标志物的开发，血沉棕黄层可能成为生物标志物组合的一部分，以便更全面地了解这种复杂疾病。
