Core B: Clinical Research Core

项目摘要：临床研究核心 帕金森病 (PD) 是第二常见的神经退行性疾病。虽然目前的治疗 减轻与 PD 相关的症状和残疾，没有任何治疗方法可以减缓或逆转神经退行性病变 过程。最近的研究表明炎症在帕金森病发病机制中发挥着重要作用。在工作的支持下 P20探索项目（NS09530），我们发现了PD动物模型中先天免疫激活的证据， 并获得了涉及人体样本免疫调节的初步数据。将这项研究扩展到 对患有帕金森病的人类受试者的炎症变化进行更完整的研究对于确定其作用至关重要 人类疾病中的炎症，从而有助于潜在免疫调节疾病的发展 修改疗法。临床研究核心的主要目标是建立一个特征良好的队列 对早期特发性帕金森病受试者进行有关神经炎症的纵向研究。这一批人将 提供将直接支持三个研究项目的临床数据、生物样本和成像数据 根据 P50 赠款提议。核心每年将招募、临床评估和跟踪 60 名年龄和性别 匹配的对照者和 60 名在 UAB 患有早期、未经治疗的特发性 PD 受试者。脑脊液、血浆和外周血 血液单核细胞 (PBMC) 将在基线时收集，血浆和 PBMC 将在基线时收集 每年进行随访。 [18F]DPA-714 PET 成像将在基线时对该队列进行评估，以评估中枢神经系统 早期炎症，特发性PD。所有参与者数据将提交给数据管理 NINDS 帕金森病生物标志物计划 (PDBP) 下的资源 (DMR)，并获得批准 生物样本将被发送到 NINDS 存储库 BioSEND。与哥伦比亚大学合作，核心 还将招募患有 PD (n=20) 和不患有 PD (n=20) 的 LRRK2 G2019S 携带者，以及 LRRK2 G2019S NON- 有 PD 的运营商 (n=20) 和无 PD 的运营商 (n=20)。先前患者的生物样本和临床数据 LRRK2 突变基因分型将直接输入到项目 3 中。

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.