Core B: Clinical Research Core

核心 B：临床研究核心

基本信息

批准号：
10469385
负责人：
Talene Alene Yacoubian
金额：
$ 31.86万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-30 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10469385
关键词：
Age Animal Model Biological Biological Markers Biological Specimen Banks Blood Cell Separation Cells Clinical Clinical Data Clinical Research Cohort Studies Collaborations Collection Data Data Management Resources Deposition Development Diagnosis Disease Female Freezing Genotype Goals Grant Human Idiopathic Parkinson Disease Image Immune Inflammation Inflammatory LRRK2 gene Longitudinal Studies Mediating Movement Disorders Mutation National Institute of Neurological Disorders and Stroke Natural Immunity Nerve Degeneration Neurodegenerative Disorders Parkinson Disease Participant Pathogenesis Patients Peripheral Blood Mononuclear Cell Pharmaceutical Preparations Pilot Projects Plasma Positron-Emission Tomography Prevalence Process Research Research Project Grants Research Support Resources Role Sampling Signal Pathway Specimen Symptoms Universities Visit Work adaptive immunity age related cohort disability experience follow-up human disease human subject immunoregulation macrophage male monocyte nervous system disorder neuroinflammation novel therapeutic intervention patient oriented research programs recruit repository response sex treatment strategy

Age Animal Model Biological Biological Markers Biological Specimen Banks Blood Cell Separation Cells Clinical Clinical Data Clinical Research Cohort Studies Collaborations Collection Data Data Management Resources Deposition Development Diagnosis Disease Female Freezing Genotype Goals Grant Human Idiopathic Parkinson Disease Image Immune Inflammation Inflammatory LRRK2 gene Longitudinal Studies Mediating Movement Disorders Mutation National Institute of Neurological Disorders and Stroke Natural Immunity Nerve Degeneration Neurodegenerative Disorders Parkinson Disease Participant Pathogenesis Patients Peripheral Blood Mononuclear Cell Pharmaceutical Preparations Pilot Projects Plasma Positron-Emission Tomography Prevalence Process Research Research Project Grants Research Support Resources Role Sampling Signal Pathway Specimen Symptoms Universities Visit Work adaptive immunity age related cohort disability experience follow-up human disease human subject immunoregulation macrophage male monocyte nervous system disorder neuroinflammation novel therapeutic intervention patient oriented research programs recruit repository response sex treatment strategy

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项目摘要

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.

项目摘要：临床研究核心帕金森氏病（PD）是第二常见的神经退行性疾病。而目前的治疗减轻与PD相关的症状和残疾，没有治疗缓慢或逆转神经退行性过程。最近的工作表明炎症在PD发病机理中的重要作用。在工作中 P20探索性项目（NS09530），我们发现了激活PD动物模型中先天免疫力的证据，并获得了将人类样品免疫调节隐含的初步数据。将这项研究扩展到对患有PD的人类受试者的炎症变化的更完整的研究对于定义的作用至关重要人类疾病的炎症，从而有助于发展潜在的免疫调节性疾病修改疗法。临床研究核心的主要目标是建立一个良好的人群早期，针对神经炎症的纵向研究的特发性PD受试者。这个队列将提供将直接支持三个研究项目的临床数据，生物测量和成像数据根据P50赠款提议。核心将每年招募，临床评估和遵循60岁和性别在UAB上，匹配的控件和60名受试者具有早期阶段，未经治疗的特发性PD。 CSF，等离子体和外围将在基线时收集血液单核细胞（PBMC），并将收集血浆和PBMC。年度后续访问。 [18F] DPA-714 PET成像将在基线的该队列上进行，以评估中央早期炎症，特发性PD。所有参与者数据将提交给数据管理 Ninds的帕金森氏病生物标志物计划（PDBP）的资源（DMR），并批准生物测量将发送到Ninds存储库生物限。与哥伦比亚大学一起，核心还将招募具有PD（n = 20）和没有PD（n = 20）的LRRK2 G2019S载体和LRRK2 G2019S非 - 具有PD（n = 20）且无PD（n = 20）的载体。以前来自患者的生物测量和临床数据在LRRK2中进行突变的基因分型将直接插入项目3中。