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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.

总结