Clinical Core

临床核心

• 批准号: 10649661
• 负责人: JOEL Synes PERLMUTTER
• 金额: $ 106.37万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-24 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10649661
• 关键词: Amyloid beta-Protein; Area; Autopsy; Autoradiography; Brain; California; Clinical; Clinical Data; Clinical Investigator; Clinical Trials Design; Cohort Studies; Collaborations; Data; Data Collection; Data Storage and Retrieval; Degenerative Disorder; Development; Devices; Diagnosis; Exclusion Criteria; Freezing; Frontotemporal Dementia; Genes; Human; Idiopathic Parkinson Disease; Image; Institution; Institutional Review Boards; International; Kinetics; Letters; Longitudinal cohort; Magnetic Resonance Imaging; Measures; Movement Disorders; Multicenter Studies; Multicenter Trials; Multiple System Atrophy; Neurodegenerative Disorders; Online Systems; Parkinson Disease; Parkinsonian Disorders; Participant; Patient Selection; Patients; Pennsylvania; Planet Mars; Positron-Emission Tomography; Process; Progressive Supranuclear Palsy; Protocols documentation; RTN4 gene; Radiopharmaceuticals; Research Personnel; Resolution; Role; San Francisco; Scheme; Selection Criteria; Site; Specificity; Standardization; Structure; Tauopathies; Testing; Tissues; Tracer; Universities; Validation; Washington; Work; alpha synuclein; brain tissue; cohort; data management; data sharing; dosimetry; experience; first-in-human; human imaging; kinetic model; method development; pre-clinical; radiotracer; safety assessment; synucleinopathy; tau Proteins; tau mutation; web-based tool

ABSTRACT This Clinical Core will implement first in human PET imaging with new radiotracers targeting α-synuclein (α-syn) and 4 repeat tau (4R tau). Radiotracers will be developed pre-clinically in the Med Chem Core and in Projects 1 and 2 focusing on α-syn and 4R tau, respectively. We will focus α-syn radiotracers on two synucleinopathies, Parkinson disease (PD) and Multiple Systems Atrophy (MSA), and focus 4R tau radiotracers on two different tauopathies, progressive supranuclear palsy (PSP) and familial frontotemporal dementias (FTD) due to mutation in Microtubule Associated Protein Tau (MAPT) gene. We will draw participants and interact with multiple ongoing clinical cohorts of FTD, PSP, PD and MSA. The Clinical Core functions include interaction with the Executive Committee to determine when to start human studies, coordinate required regulatory activities for radiotracer candidates, carry out early safety assessments including whole body dosimetry studies at Penn; coordinate patient selection criteria, centrally collect and serve all imaging and demographic data, coordinate tracer kinetic methods development and validation for human imaging, and coordinate all data to efficiently enable GO-NOGO decisions for candidate radiotracers. Radiotracers for α-syn will be tested in two different synucleinopathies, PD and MSA whereas, 4R tau radiotracers will be tested in PSP and FTD patients. As a final check on diagnosis and specificity of candidate radiotracers, we will request all patient participants to permit postmortem brain donation for autoradiography of relevant radiotracers on fresh frozen brain tissues. Additionally, this Core will interact with multiple ongoing studies with cohorts studying PD, MSA, PSP and FTD. Finally, a robust data sharing plan facilitates collaboration and use of support documents and imaging data.

摘要 该临床核心将首先在人体PET成像中使用靶向α-突触核蛋白（α-syn）的新型放射性示踪剂 和4个重复tau（4 R tau）。放射性示踪剂将在Med Chem Core和项目中进行临床前开发 1和2分别聚焦于α-syn和4 R tau。我们将α-syn放射性示踪剂集中在两种突触核蛋白病， 帕金森病（PD）和多系统萎缩（MSA），并将4 R tau放射性示踪剂集中在两种不同的 突变导致的tau蛋白病、进行性核上性麻痹（PSP）和家族性额颞叶痴呆（FTD） 微管相关蛋白Tau（MAPT）基因。我们将吸引参与者，并与多个正在进行的互动 FTD、PSP、PD和MSA的临床队列。 临床核心职能包括与执行委员会互动，以确定何时开始人类 研究，协调放射性示踪剂候选物所需的监管活动，进行早期安全评估 包括在Penn进行的全身剂量测定研究;协调患者选择标准，集中收集和服务 所有成像和人口统计学数据，坐标示踪剂动力学方法的开发和验证， 成像，并协调所有数据，以有效地实现候选放射性示踪剂的GO-NOGO决策。 α-syn的放射性示踪剂将在两种不同的突触核蛋白病PD和MSA中进行测试，而4 R tau 将在PSP和FTD患者中检测放射性示踪剂。作为对候选人诊断和特异性的最后检查 放射性示踪剂，我们将要求所有患者参与者允许死后大脑捐赠用于放射自显影， 新鲜冷冻脑组织的放射性示踪剂。此外，该核心将与多个正在进行的 PD、MSA、PSP和FTD队列研究。最后，强大的数据共享计划有助于协作 以及使用支持文件和成像数据。