Center without Walls for Imaging Proteinopathies with PET (CW2IP2)

PET 蛋白病成像无壁中心 (CW2IP2)

基本信息

批准号：
10649656
负责人：
ROBERT H MACH
金额：
$ 397.46万
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/10649656
关键词：
Applications Grants Binding California Central Nervous System Diseases Clinical Clinical Investigator Collaborations Communication Complex Development Faculty Fostering Frontotemporal Dementia Goals Group Structure Heart Histologic Image Imaging ligands Imaging technology In Vitro Individual Infrastructure Institution International Investigational Drugs Knowledge Lead Libraries Ligands Methods Mission Multiple System Atrophy Names National Institute of Neurological Disorders and Stroke National Institute on Aging Nerve Degeneration Neurobiology Neurodegenerative Disorders Neurology Neurosciences Parkinson Disease Participant Pathology Pennsylvania Performance Pharmaceutical Chemistry Positioning Attribute Positron-Emission Tomography Progressive Supranuclear Palsy Radiochemistry Radiology Specialty Research Research Contracts Research Personnel Research Project Grants Resource Sharing Resources Role San Francisco Schedule Scientific Advances and Accomplishments Site Structure-Activity Relationship Tauopathies Translational Research Universities Validation Variant Washington age related neurodegeneration alpha synuclein brain tissue dosimetry first-in-human frontotemporal degeneration high throughput screening image translation imaging study in silico in vitro Assay innovation instrumentation meetings member misfolded protein multidisciplinary neuropathology novel professor programs protein aggregation radiotracer screening shared database structural biology synucleinopathy tau Proteins translational impact

项目摘要

OVERALL ABSTRACT The application describes the creation of a new center that will focus on the development of Positron Emission Tomography (PET) ligands for imaging two proteinopathies: 1) alpha synuclein (Asyn) for imaging the synucleinopathies Parkinson's disease and multiple system atrophy; and, 2) 4R tau for imaging the 4R tauopathies frontotemporal degeneration and progressive supranuclear palsy. The name of the proposed center is the Center without Walls for Imaging Proteinopathies with PET (CW2IP2), and represents a multi-institutional collaborative effort between the University of Pennsylvania, Washington University-St. Louis, University of Pittsburgh, University of California-San Francisco, Yale University, and the contract research organization, MedChem Imaging. The organization of this Center without Walls is highly innovative and unique for a variety of reasons: 1) it engages faculty members at the University of Pennsylvania having an international reputation in the fields of neurobiology (V. Lee, K. Luk), neuropathology (J. Trojanowski), and structural biology (E.J. Petersson; V. Moiseenkova-Bell) of the proteinopathies into the field of PET radiotracer development for imaging aggregated Asyn and 4R tau; 2) it involves the collaboration of PET radiochemists at Penn (RH Mach), Pitt (C. Mathis), Wash U (Z. Tu) and MedChem Imaging (N. Vasdev) who are experts in the field of CNS radiotracer development; and 3) it involves the multi-site collaboration of clinical investigators who are experts in the use of PET to study CNS disorders (J Perlmutter (Wash U), R. Carson (Yale), G. Rabinovici (UCSF), A. Siderowf (Penn)). This multi-institutional collaboration not only meets the criteria described in the RFA for the Creation of a Center without Walls, but the participation of individuals having such diverse scientific backgrounds will be essential for successfully accomplishing the scientific objectives of this RFA. The PI of the Center is Robert H. Mach, the Britton Chance Professor of Radiology at Penn. The center consists of an Administrative Core and two research cores: Medicinal Chemistry and Radiochemistry and the Clinical Core. The cores have been organized such that there is an overall Core Director or Co-Director, and a site Director at each of the sites participating in the Core activities. There are two research projects in this U19 Center, each focused on studies aimed at validation probes developed by the Medicinal Chemistry and Radiochemistry Core for a proteinopathy (Project 1/Asyn and Project 2/4R tau). This U19 Center will also implement a broad-based Data and Resource Sharing Plan that will be of benefit to clinical investigators in the US who are conducting research relevant to the scientific mission of the NINDS and NIA. We anticipate that the Center without Walls for Imaging Proteinopathies with PET (CW2IP2) will lead to a significant expansion of NINDS- and NIA-based translational research at the national level, and will advance our knowledge on the role of Asyn and 4R tau in neurodegeneration.

总体抽象该应用程序描述了一个新中心的创建，该中心将重点放在正电子的发展上用于成像两种蛋白质病的发射断层扫描（PET）配体：1）α突触核蛋白（ASYN）用于成像帕金森氏病和多系统萎缩的突触核酸疾病； 2）4r tau for 成像4R扭曲的额颞变性和进行性上核麻痹。名字所提出的中心是没有壁的中心，用于用PET（CW2IP2）成像蛋白质病（CW2IP2），并代表宾夕法尼亚大学之间的多机构合作努力华盛顿大学圣。路易斯，匹兹堡大学，加利福尼亚大学弗朗西斯科分校，耶鲁大学大学和合同研究组织Medchem Imaging。这个中心的组织没有墙是高度创新性和独特的，其原因是：1）它与教师接触宾夕法尼亚大学在神经生物学领域享有国际声誉（V. Lee，K。 LUK），神经病理学（J. Trojanowski）和结构生物学（E.J. Petersson； V。Moiseenkova-Bell）蛋白质病进入PET放射性示踪剂发育领域，用于成像汇总ASYN和4R tau; 2）它涉及佩恩（Rh Mach），皮特（C. Mathis），Wash U （Z. tu）和Medchem Imaging（N。Vasdev）是CNS Radiotracer开发领域的专家； 3）它涉及临床研究人员的多站点合作，他们是使用PET的专家研究CNS疾病（J Perlmutter（Wash U），R。Carson（Yale），G。Rabinovici（UCSF），A。Siderowf （Penn））。这种多机构合作不仅符合RFA中描述的标准创建一个没有墙壁的中心，但具有如此多样化科学的个人的参与背景对于成功实现此RFA的科学目标至关重要。 pi 该中心的是宾夕法尼亚州布里顿偶然的放射学教授罗伯特·H·马赫（Robert H. Mach）。中心包括行政核心和两个研究核心：药物化学和放射化学和临床核心。核心已经组织起来，以至于有一个总体核心主任或联合导演，以及参加核心活动的每个站点的站点主管。有两个研究项目在这个U19中心，每个中心都集中在旨在由药用的验证探针的研究上蛋白质病的化学和放射化学核心（项目1/ASYN和项目2/4R TAU）。这 U19中心还将实施基于广泛的数据和资源共享计划，这将有益于美国正在进行与与科学任务有关的研究的临床研究者 Ninds和Nia。我们预计中心没有墙壁用于宠物的蛋白质病成像（CW2IP2）将导致基于NINDS和NIA的转化研究的显着扩展国家一级，并将促进我们对Asyn和4r Tau在神经变性中的作用的了解。