PDF(Pubmed)
Abstract：
Niemann-Pick disease type C (NPC) is an autosomal recessive, progressive disorder resulting from variants in NPC1 or NPC2 that leads to the accumulation of cholesterol and other lipids in late endosomes and lysosomes. The clinical manifestations of the disease vary by age of onset, and severity is often characterized by neurological involvement. To date, no disease-modifying therapy has been approved by the United States Food and Drug Administration (FDA) and treatment is typically supportive. The lack of robust biomarkers contributes to challenges associated with disease monitoring and quantifying treatment response. In recent years, advancements in detection methods have facilitated the identification of biomarkers in plasma and cerebral spinal fluid from patients with NPC, namely calbindin D, neurofilament light chain, 24(S)hydroxycholesterol, cholestane-triol, trihydroxycholanic acid glycinate, amyloid-β, total and phosphorylated tau, and N-palmitoyl-O-phosphocholine-serine. These biomarkers have been used to support several clinical trials as pharmacodynamic endpoints. Despite the significant advancements in laboratory techniques, translation of those advancements has lagged, and it remains unclear which biomarkers correlate with disease severity and progression, or which biomarkers could inform treatment response. In this review, we assess the landscape of biomarkers currently proposed to guide disease monitoring or indicate treatment response in patients with NPC.
摘要：
尼曼-皮克病C型（NPC）是一种常染色体隐性遗传，由NPC1或NPC2变异导致的进行性疾病，导致胆固醇和其他脂质在晚期内体和溶酶体中积累。该疾病的临床表现因发病年龄而异，严重程度通常以神经系统受累为特征。迄今为止,美国食品和药物管理局(FDA)尚未批准任何疾病改善疗法,治疗通常是支持性治疗.缺乏强大的生物标志物导致与疾病监测和量化治疗反应相关的挑战。近年来,检测方法的进步促进了NPC患者血浆和脑脊液中生物标志物的鉴定，即CalbindinD,神经丝轻链，24（S）羟基胆固醇，胆甾烷三醇，三羟基胆酸甘氨酸，淀粉样蛋白-β，总和磷酸化的tau，和N-棕榈酰-O-磷酸胆碱-丝氨酸。这些生物标志物已被用于支持几个临床试验作为药效学终点。尽管实验室技术取得了重大进展，这些进步的翻译已经滞后，目前尚不清楚哪些生物标志物与疾病的严重程度和进展相关，或者哪些生物标志物可以告知治疗反应。在这次审查中,我们评估了目前建议用于指导NPC患者疾病监测或治疗反应的生物标志物的概况.
