Clinically Relevant Biomarkers for Niemann-Pick Type C

项目摘要 C型尼曼匹克（NPC）是一种常染色体隐性遗传的溶酶体贮积症，伴有进行性 神经退行性疾病和没有FDA批准的治疗。在过去的十年里，我们的研究团队致力于 努力建立一个强大的自然历史研究沿着努力，以确定生物标志物，以提高我们的 了解疾病。在这个项目中，我们将利用我们互补的专业知识来定义一个目录 生物标志物，以促进未来的临床试验。我们将描述的生物标志物将最终提供 关于疾病进展、预后的信息与NPC中常见的受影响途径相关， 可以预测治疗效果为了实现这一目标，我们将1）优先考虑和验证反映生物标志物 神经病理学改变，2）鉴定和表征NPC的近端生物标志物1，然后3）研究 多种生物标志物，代表NPC 1神经病理学的不同方面，以提供预后信息 可以用于父母咨询，并对这种异质性疾病进行分层，用于治疗试验。我们 研究小组的广泛发现工作已经揭示了十二个候选标记。在此范围内， 项目是我们的短期目标，使用定制的生物样本在更大的生物样本队列中评估这些标记物。 开发和易于移植的方法。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。

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.