Core B: Clinical Research Core

项目摘要：临床研究核心 帕金森病(PD)是第二种最常见的神经退行性疾病。虽然目前的治疗方法 缓解与帕金森病相关的症状和残疾，没有治疗方法减缓或逆转神经退行性变 进程。最近的研究表明，炎症在帕金森病的发病机制中起着重要作用。在该委员会支持的工作中 P20探索性项目(NS09530)，我们在PD动物模型中发现了天然免疫激活的证据， 并获得了人体样本中涉及免疫调节的初步数据。将这项研究扩展到 对帕金森病患者炎症变化的更全面的研究对于确定帕金森病的作用至关重要 人类疾病中的炎症，从而有助于潜在的免疫调节性疾病的发展 修改治疗方法。临床研究核心的主要目标是建立一个具有良好特征的队列 对早期特发性帕金森病受试者进行神经炎症的纵向研究。这一批人将 提供将直接支持这三个研究项目的临床数据、生物显微镜和成像数据 在P50拨款下提出的。核心将招募，临床评估，并每年跟踪60岁--和性别-- 配对的对照组和60名UAB的早期、未经治疗的特发性帕金森病患者。脑脊液、血浆和外周 血液单个核细胞(PBMC)将在基线时采集，血浆和PBMCs将在 每年一次的后续访问。[18F]将在基线时对该队列进行DPA-714 PET成像，以评估 早期炎症，特发性帕金森病。所有参与者数据将提交给数据管理部门 NINDS帕金森氏病生物标记物计划(PDBP)下的资源(DMR)，并获得批准 生物样品将被发送到NINDS信息库BioSEND。与哥伦比亚大学合作，核心 还将招募患有PD(n=20)和没有PD(n=20)的LRRK2 G2019S携带者，以及LRRK2 G2019S非PD携带者 PD携带者(n=20)和无PD携带者(n=20)。以前患者的生物样本和临床数据 LRRK2基因突变的基因分型将直接进入项目3。

PROJECT SUMMARY: CLINICAL RESEARCH CORE Parkinson’s disease (PD) is the second most common neurodegenerative disorder. While current treatments mitigate the symptoms and disability associated with PD, no treatments slow or reverse the neurodegenerative process. Recent work points to a significant role for inflammation in PD pathogenesis. In work supported by the P20 Exploratory Project (NS09530), we found evidence for activation of innate immunity in animal models of PD, and obtained preliminary data implicating immunomodulation in human samples. Expanding this research to a more complete study of inflammatory changes in human subjects with PD is essential to define the role of inflammation in human disease and thus aid in the development of potential immunomodulatory disease modifying therapies. The primary goal of the Clinical Research Core is to establish a well-characterized cohort of early stage, idiopathic PD subjects for longitudinal study with regard to neuroinflammation. This cohort will provide clinical data, biospecimens, and imaging data that will directly support the three research projects proposed under the P50 grant. The Core will recruit, clinically assess, and follow annually 60 age- and sex- matched controls and 60 subjects with early stage, untreated, idiopathic PD at UAB. CSF, plasma, and peripheral blood mononuclear cells (PBMCs) will be collected at baseline, and plasma and PBMCs will be collected at annual follow-up visits. [18F]DPA-714 PET imaging will be performed on this cohort at baseline to assess central inflammation in early stage, idiopathic PD. All participant data will be submitted to the Data Management Resource (DMR) under the NINDS’ Parkinson’s disease Biomarker Program (PDBP), and approved biospecimens will be sent to the NINDS repository BioSEND. In conjunction with Columbia University, the Core will also recruit LRRK2 G2019S carriers with PD (n=20) and without PD (n=20), and LRRK2 G2019S NON- carriers with PD (n=20) and without PD (n=20). Biospecimens and clinical data from patients previously genotyped for mutations in LRRK2 will feed directly into Project 3.