Biomarkers for parkinsonian disorders in CNS-originating extracellular vesicles

中枢神经系统来源的细胞外囊泡中帕金森病的生物标志物

基本信息

批准号：
10662918
负责人：
GAL BITAN
金额：
$ 237.47万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-04-01 至 2026-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10662918
关键词：
Address Agreement Anxiety Autonomic Dysfunction Autopsy Behavior Disorders Biochemical Biological Markers Blood Blood Tests Brain Caregivers Cells Central Nervous System Central Nervous System Diseases Cerebrospinal Fluid Cessation of life Clinic Clinical Clinical Trials Confusion Consult Data Dementia Dementia with Lewy Bodies Development Diagnosis Diagnostic tests Disease Disease Progression Family Future Goals Immunoprecipitation Intervention Lead Left Light Measures Methodology Modeling Movement Disorders Multiple System Atrophy Nature Neural Cell Adhesion Molecule L1 Neurodegenerative Disorders Neurologic Neurologist Neurons New York Oligonucleotides Parkinson Disease Parkinsonian Disorders Pathologic Patients Periodicity Physicians Plasma Positron-Emission Tomography Progressive Supranuclear Palsy Protocols documentation Public Health REM Sleep Radioisotopes Reporting Research Research Design Sampling Sampling Studies Sensitivity and Specificity Serum Specialist Specificity Spinal Puncture Stress Symptoms Tauopathies Testing Training Translating Universities Validation alpha synuclein biobank biomarker panel biomarker performance brain tissue candidate marker cohort corticobasal syndrome cost effective diagnostic accuracy diagnostic tool diagnostic value effective therapy experience extracellular vesicles imaging biomarker improved inclusion criteria liquid biopsy minimally invasive neurofilament patient response patient stratification prospective single photon emission computed tomography success sulfated glycoprotein 2 synucleinopathy tau Proteins

项目摘要

Summary Many cases of Parkinson’s disease, and even more so atypical parkinsonian disorders, are misdiagnosed. Misdiagnosis not only causes high stress and anxiety to patients, their families, and their caregivers, but also is a major impediment to development of effective therapy for these diseases. Recently, we have demonstrated that the α-synuclein concentration in extracellular vesicles (EVs) immunoprecipitated from serum or plasma using oligodendroglial and neuronal markers, and in particular the ratio between the α-synuclein concentrations in the two types of EVs, is a sensitive biomarker for distinguishing between Parkinson’s disease and multiple system atrophy. This liquid biopsy approach requires only a minimally invasive blood draw and could lead to a major advancement in developing diagnostic tests for these diseases. Here, we propose to build upon these recent findings by constructing a biomarker panel, including several additional candidate markers, and apply the panel to two additional atypical parkinsonian syndromes—progressive supranuclear palsy and corticobasal syndrome. Serum samples for the study will be obtained from several national biorepositories as well as collected locally, prospectively, in expert clinics. The study design emphasizes biomarker analysis within the first two years of diagnosis, and in prodromal synucleinopathy, to test the utility of the biomarker panel when it is most needed. An additional goal of the project is to develop methodology for validating the cellular origin of the EVs, an urgent unmet need in the field. Success of the project will lead both to an advancement of research on biomarkers for CNS diseases using a minimally invasive liquid biopsy that can be translated into clinical use in the near future.

概括许多病例帕金森氏病，甚至更加非典型的帕金森氏症。误诊不仅会给患者，家人和他们的照顾者引起高压力和焦虑，而且还对这些疾病有效疗法开发的主要障碍。最近，我们已经证明了使用血清或血浆免疫沉淀的细胞外蔬菜（EV）中的α-突触核蛋白浓度使用少突胶质和神经元标记物，尤其是α-突触核蛋白浓度之间的比率两种类型的电动汽车是一种敏感的生物标志物，可区分帕金森氏病和多个系统萎缩。这种液体活检方法只需要微创的血液抽血，并且可能导致大专业开发这些疾病的诊断测试的进步。在这里，我们建议以这些最新这些通过构建生物标志物面板（包括几个其他候选标记）并应用面板来调查结果再加上另外两个非典型帕金森氏综合症 - 促进性超麻痹和皮质疾病综合征。该研究的血清样品将从几个国家生物症剂中获得，并在本地收集，前瞻性地，在专业诊所。研究设计强调了生物标志物分析的前两年诊断和前驱突触核力疗法，以在最需要的情况下测试生物标志物面板的效用。该项目的另一个目标是开发验证电动汽车细胞起源的方法论，这是紧急的现场未满足的需求。该项目的成功将导致对生物标志物研究的进步 CNS疾病使用微创液体活检，可以在不久的将来转化为临床用途。