Clinically Relevant Biomarkers for Niemann-Pick Type C

项目摘要 Niemann-Pick C型(NPC)是一种常染色体隐性遗传性溶酶体储存障碍，具有进行性 神经退行性变，没有FDA批准的治疗。在过去的十年里，我们的研究团队致力于 努力建立强有力的自然历史研究，同时努力识别生物标记物，以增强我们的 对疾病的了解。在这个项目中，我们将利用我们互补的专业知识来定义目录 生物标记物，以促进未来的临床试验。我们将描述的生物标记物最终将提供 有关疾病进展、预后的信息与鼻咽癌和 将预测治疗反应。为了实现这一目标，我们将1)优先考虑和验证生物标志物 神经病理改变，2)识别和表征NPC1近端生物标志物，然后3)调查 多个生物标志物，代表NPC1神经病理的不同方面，提供预后信息 这可以用于父母咨询，并在治疗试验中对这种异质性障碍进行分层。我们的 研究团队的广泛发现工作已经揭示了12个候选标记。在本文件的范围内 我们的短期目标是在更大的生物样本队列中评估这些标记，使用自定义 开发的、易于转让的方法。我们的长期目标是利用这些生物标志物作为 在未来的临床试验中的反应。

Project Summary Niemann-Pick Type C (NPC) is an autosomal recessive, lysosomal storage disorder with progressive neurodegeneration and no FDA-approved therapy. Over the past decade, our research team has dedicated efforts to establishing a robust Natural History Study along with efforts to identify biomarkers to enhance our understanding of the disease. In this project, we will leverage our complementary expertise to define a catalog of biomarkers to facilitate future clinical trials. The biomarkers that we will characterize will ultimately provide information on disease progression, prognosis, are associated with commonly affected pathways in NPC and will predict therapeutic response. Towards this goal, we will 1) prioritize and validate biomarkers that reflect neuropathological alterations, 2) identify and characterize proximal biomarkers of NPC1 then 3) investigate multiple biomarkers, representing different aspects of NPC1 neuropathology, to provide prognostic information that can be used in parental counseling and to stratify this heterogeneous disorder for therapeutic trials. Our research team’s extensive discovery efforts have revealed twelve candidate markers. Within the scope of this project is our short-term goal to evaluate these markers in a larger cohort of biospecimens using custom developed and easily transferrable methods. Our long-term goal is to utilize these biomarkers as indicators of response in future clinical trials.