Clinical and imaging biomarker evolution of early progressive supranuclear palsy

早期进行性核上性麻痹的临床和影像生物标志物演变

• 批准号: 9295620
• 负责人: RICHARD TSAI
• 金额: $ 17.56万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-15 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9295620
• 关键词: Aging; Alzheimer' s Disease; Aphasia; Area; Atrophic; Autopsy; Basal Ganglia; Behavioral; Behavioral Symptoms; Biological; Biological Markers; Biometry; Brain Stem; California; Categories; Clinical; Clinical Research; Clinical Trials; Cognition Disorders; Cognitive; Correlation Studies; Coupled; Data; Dementia; Dentate nucleus; Development; Diagnosis; Diagnostic; Diffusion Magnetic Resonance Imaging; Disease; Disease Progression; Evolution; Face; Freezing; Frontotemporal Dementia; Frontotemporal Lobar Degenerations; Future; Gait; Goals; Heterogeneity; Image; Image Analysis; Imaging Techniques; Incidence; International; Investigation; Knowledge; Learning; Ligands; MRI Scans; Magnetic Resonance Imaging; Measures; Memory; Mentored Patient-Oriented Research Career Development Award; Mentors; Methodology; Molecular; Monitor; Movement; Natural History; Nerve Degeneration; Neurodegenerative Disorders; Neurologist; Neurology; Outcome; Paralysed; Parkinsonian Disorders; Pathologic; Pathology; Phenotype; Positron-Emission Tomography; Progressive Supranuclear Palsy; Research; Research Design; Research Personnel; Research Project Grants; Resources; San Francisco; Series; Severities; Substantia nigra structure; Symptoms; Syndrome; Tauopathies; Therapeutic; Therapeutic Clinical Trial; Universities; Variant; amyloid pathology; base; career; cerebral atrophy; clinical biomarkers; clinical imaging; disability; effective therapy; experience; falls; gaze palsy; illness length; imaging biomarker; imaging program; in vivo; innovation; molecular imaging; motor symptom; neuroimaging; novel; novel diagnostics; patient oriented; pharmacodynamic biomarker; professor; programs; research clinical testing; tau Proteins; treatment effect; uptake; white matter

ABSTRACT This is an application for a K23 award for Dr. Richard Tsai, an Assistant Adjunct Professor of Neurology at the University of California, San Francisco (UCSF) Memory and Aging Center (MAC). Dr. Tsai's proposal to conduct clinical research on the clinical and imaging evolution of early progressive supranuclear palsy (ePSP) will help him achieve his goal of becoming an independent investigator and expert in neurodegenerative disease imaging and clinical trials methodology. This K23 will provide Dr. Tsai with the resources and support essential to accomplish the following goals: (1) to become an expert at patient-oriented clinical research in primary tauopathies such as PSP; (2) to advance his knowledge of clinical trials methodology and biostatistics; (3) to implement structural (volumetric MRI, diffusion tensor imaging) and molecular (tau positron emission tomography [PET]) imaging techniques in clinical studies and trials of primary tauopathies; (4) to develop an independent career in clinical research. To achieve these goals, Dr. Tsai has assembled a mentoring team of two primary mentors: Dr. Adam Boxer, director of the Alzheimer's Disease and Frontotemporal Dementia Clinical Trials Program and one of the world's experts in PSP, Dr. Gil Rabinovici, director of the MAC PET imaging program and one of the world's expert on molecular imaging in dementia. The mentoring team also includes two collaborators: Dr. Howard Rosen, a neurologist with expertise in neuroimaging in cognitive disorders and Dr. Iryna Lobach, a statistician who is an expert in study design and biostatistical analysis. There is an urgent need for effective therapy in neurodegenerative disease, and current experience indicates potential disease modifying therapies should begin in early stages of disease. The proposed research project will apply advanced structural MR imaging and molecular imaging techniques using novel tau PET ligands to evaluate the clinical evolution of ePSP. Dr. Tsai will characterize the clinical evolution ePSP, a new diagnostic category (Aim 1) and develop innovative imaging biomarkers using volumetric MRI, diffusion tensor imaging and tau PET imaging (Aim 2) that may one day be used as outcomes in therapeutic clinical trials. Additionally, Dr. Tsai will identify baseline signatures (Aim 3) of these imaging measures that may predict ePSP disease progression. This research will be a key step in a series of investigation that will develop longitudinal imaging biomarkers for PSP and other neurodegenerative disease in their early stages, and pave the way for the field to establish disease monitoring biomarkers useful for future clinical trials.

抽象的 这是理查德·蔡 (Richard Tsai) 博士的 K23 奖项申请，他是神经病学助理教授。 加州大学旧金山分校 (UCSF) 记忆与衰老中心 (MAC)。蔡博士的建议 对早期进行性核上性麻痹（ePSP）的临床和影像学演变进行临床研究 将帮助他实现成为神经退行性疾病独立研究者和专家的目标 疾病成像和临床试验方法。此次K23将为蔡博士提供资源和支持 实现以下目标至关重要：（1）成为以患者为导向的临床研究专家 原发性tau蛋白病，例如PSP； (2) 提高临床试验方法和生物统计学知识； (3) 实施结构（体积MRI、扩散张量成像）和分子（tau正电子发射） 断层扫描 [PET]）原发性 tau 蛋白病临床研究和试验中的成像技术； (4) 开发一个 独立从事临床研究。为了实现这些目标，蔡博士组建了一支由以下人员组成的指导团队： 两位主要导师：Adam Boxer 博士，阿尔茨海默病和额颞叶痴呆主任 临床试验项目、世界 PSP 专家之一、MAC PET 主任 Gil Rabinovici 博士 成像项目和世界痴呆症分子成像专家之一。辅导团队还 包括两名合作者：霍华德·罗森 (Howard Rosen) 博士，一位神经学家，在认知神经影像学方面拥有专业知识 疾病和统计学家 Iryna Lobach 博士是研究设计和生物统计分析方面的专家。 神经退行性疾病迫切需要有效的治疗方法，目前的经验表明 潜在的疾病修饰疗法应在疾病的早期阶段开始。拟议的研究项目 将应用先进的结构 MR 成像和分子成像技术，使用新型 tau PET 配体 评估 ePSP 的临床演变。蔡博士将描述 ePSP 的临床演变，这是一种新的诊断方法 类别（目标 1）并使用体积 MRI、扩散张量成像开发创新的成像生物标志物 tau PET 成像（目标 2）有一天可能会被用作治疗性临床试验的结果。此外， Tsai 博士将确定这些可预测 ePSP 疾病的影像学测量的基线特征（目标 3） 进展。这项研究将是开发纵向成像的一系列研究的关键一步 PSP 和其他神经退行性疾病早期阶段的生物标志物，并为该领域铺平道路 建立对未来临床试验有用的疾病监测生物标志物。