Clinical Core

临床核心

基本信息

批准号：
10241511
负责人：
JOEL Synes PERLMUTTER
金额：
$ 82.78万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
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/10241511
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 Lead 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 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 base 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

项目摘要

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.

抽象的该临床核心将首先在人类PET成像中实施，新的放射性示意剂靶向α-突触核蛋白（α-Syn）和4个重复tau（4r tau）。放射性示例将在Med Chem核心和项目中进行临时开发 1和2分别关注α-Syn和4R Tau。我们将把α-syn radiotracer聚焦于两种突触核酸病变，帕金森病（PD）和多个系统萎缩（MSA），并将重点4R tau放射性示例放在两个不同的由于突变而导致的tauopathies，进行性超跨因麻痹（PSP）和家族额颞痴呆（FTD）在微管相关蛋白tau（MAPT）基因中。我们将吸引参与者并与多个正在进行的 FTD，PSP，PD和MSA的临床队列。临床核心功能包括与执行委员会的互动以确定何时开始人类研究，协调候选放射性示例的要求调节活动，进行早期安全评估包括宾夕法尼亚州的全身剂量学研究；协调患者选择标准，集中收集和服务所有成像和人口统计数据，协调示踪剂动力学方法的开发和对人的验证成像并协调所有数据，以有效地为候选放射性示踪剂做出NOGO决策。 α-syn的放射性示例将在两种不同的突触核苷病（PD和MSA）中进行测试，而4R tau PSP和FTD患者将测试放射性示例。作为诊断和候选人特异性的最终检查放射性示例，我们将要求所有患者参与者允许尸体脑捐赠新鲜冷冻脑组织的相关放射性示例。此外，该核心将与多个正在进行的研究PD，MSA，PSP和FTD的研究。最后，强大的数据共享计划设施合作并使用支持文档和成像数据。