Johns Hopkins Medicine Biomarker Discovery in Parkinson's Disease

约翰霍普金斯大学医学帕金森病生物标志物的发现

• 批准号: 9116479
• 负责人: Ted M. Dawson
• 金额: $ 9万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-30 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9116479
• 关键词: ABL1 gene; Address; Adverse effects; Autopsy; Biological Assay; Biological Markers; Blood; Brain; Centers of Research Excellence; Cerebrospinal Fluid; Cessation of life; Clinic; Clinical; Clinical Treatment; Clinical assessments; Cognition; Cognitive; Consensus; Data; Diagnosis; Diagnostic; Digestion; Disease; Disease Marker; Disease Progression; Foxes; Future; Guidelines; Health; Individual; Investigation; Lead; Lewy Bodies; Longitudinal Studies; Mass Spectrum Analysis; Medicine; Methods; Motor; Movement Disorders; Parkinson Disease; Participant; Pathogenesis; Pathologic; Patients; Peptides; Phase II Clinical Trials; Physicians; Post-Translational Protein Processing; Proteins; Proteomics; Recruitment Activity; Research; Research Personnel; Site; Sleep; Smell Perception; Source; Staging; Standardization; Symptoms; System; Testing; Time; Trypsin; Tyrosine; Tyrosine Phosphorylation; alpha synuclein; c-abl Proto-Oncogenes; clinical Diagnosis; cognitive testing; cohort; improved; improved functioning; inhibitor/antagonist; mass spectrometer; mortality; multiple reaction monitoring; novel; parkin gene/protein; programs; progression marker; research clinical testing; success; synuclein

DESCRIPTION (provided by applicant): We are seeking to improve the diagnosis and treatment of patients with Parkinson disease (PD). Five years of support will allow us to characterize a cohort of patients throughout the PD disease spectrum and matched healthy controls in a systematic and generalizable manner, and then obtain their blood and cerebrospinal fluid (CSF) to identify biomarkers. We will assess whether specific posttranslational modifications to c-Abl, a-synuclein, parkin and parkin substrates (AIMP2, FBP-1 and PARIS) are potential biomarkers. Our clinical and cognitive testing and our biofluid ascertainment methods will follow guidelines from the RFA-NS-1211, the Michael J. Fox Parkinson's Progression Markers Initiative (PPMI), and the consensus opinion of the Udall Centers regarding cognitive testing. The clinical characterization will include extensive motor testing as well as assessments of many of the non-motor facets of PD, including cognition, sleep, and smell. Many of our study participants will have agreed to autopsy through their participation in the Johns Hopkins Medicine Morris K. Udall Center of Parkinson Disease Research of Excellence, allowing for confirmation of their clinical diagnosis and further investigation of the biomarkers that we identify. The blood will be obtained every 6 months at the time of clinical characterization and the CSF will be obtained yearly. Success of the clinical characterization will allow for a cohort of well-characterized individuals with blood and CSF that others and we may correlate with markers in their blood and CSF. Multiple reaction monitoring mass spectrometric assays using a Perfinity workstation inline to a Thermo Vantage triple quadrupole mass spectrometer with on-column trypsin digestion will be used to identify specific posttranslational modifications (PTMs) to proteins integral to PD pathogenesis to differentiate individuals with PD from healthy controls and if these PTMs and proteins integral to PD follow the clinical progression of PD. Success of the biomarker testing will determine if these peptides are diagnostic or progression markers for PD.

描述（由申请人提供）：我们正在寻求改善帕金森病（PD）患者的诊断和治疗。五年的支持将使我们能够在整个PD疾病谱系中表征一系列患者，并以系统性和可推广的方式匹配健康对照，然后获得其血液和脑脊液（CSF）以识别生物标志物。我们将评估对C-ABL，A-核蛋白，Parkin和Parkin底物（AIMP2，FBP-1和巴黎）的特定翻译后修饰是否是潜在的生物标志物。我们的临床和认知测试以及生物流体确定方法将遵循RFA-NS-1211，Michael J. Fox Parkinson的进步标记倡议（PPMI）的准则，以及Udall中心关于认知测试的共识。临床表征将包括广泛的运动测试以及对PD的许多非运动方面的评估，包括认知，睡眠和气味。我们的许多研究参与者将通过参加Johns Hopkins Medicine Morris K. Udall帕金森氏病研究中心的尸检，允许确认其临床诊断并进一步研究我们确定的生物标志物。临床表征时将每6个月获得每6个月的血液，并且CSF将每年获得。临床表征的成功将允许与其他人的血液和脑脊液中熟悉的人群，我们可能与他们的血液和CSF中的标记相关。多元反应监测的质谱测定法使用纯粹的工作站内线与具有柱胰蛋白酶消化的热维特三倍四极杆质谱仪进行，将用于鉴定特定的翻译后修饰（PTM），以与PD的pd clations和pd conters conters contect and pd conts conts conts conts conts and pd conts conts and pd conts conts conts and pd conts conts and pd contect and pd conts contect and pds contect and pts contects and pts和PD。生物标志物测试的成功将确定这些肽是PD的诊断或进展标记。