BIOMARKERS FOR PRECLINICAL PARKINSON?S DISEASE

临床前帕金森病的生物标志物

• 批准号: 8357570
• 负责人: Yoland Smith
• 金额: $ 3.29万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357570
• 关键词: Animals; Appearance; Biological Markers; Cerebrospinal Fluid; Cessation of life; Collaborations; Corpus striatum structure; Data; Denervation; Development; Disease; Dopamine; Funding; Goals; Grant; Human; Image; Ligands; Measurement; Measures; Midbrain structure; Monkeys; Motor; National Center for Research Resources; Neurodegenerative Disorders; Parkinson Disease; Patients; Pharmaceutical Preparations; Positron-Emission Tomography; Primates; Principal Investigator; Process; Proteomics; Research; Research Infrastructure; Resources; Risk; Serum; Source; Spinal Tap; Symptoms; Therapeutic; United States National Institutes of Health; Universities; Washington; brain tissue; cost; dopamine transporter; dopaminergic neuron; motor deficit; neuron development; pre-clinical; prevent

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Parkinson's disease is a progressive neurodegenerative disorder that starts many years prior to the appearance of the first motor symptoms. Thus, if one could intervene early in the disease process to slow down or reverse the progressive degeneration of midbrain dopaminergic neurons, it could have a significant impact on the development of the disease. The goal of this project is to identify preclinical biomarkers that would give the opportunity to pre-treat at risk patients with neuroprotective therapeutic drugs, which could significantly delay or even prevent the death of dopaminergic neurons and the development of motor deficits. In collaboration with Dr Jing Zhang at the University of Washington, this project aims at identifying such biomarkers using proteomics approach from the serum, cerebrospinal fluid and brain tissue in MPTP-treated monkeys. Although no data have yet been collected in this project, a total of 10 monkeys have been treated with MPTP until they reach about 30-40% ("asymptomatic group") or 70-80% ("symptomatic group") striatal dopamine loss, as measured using PET scan imaging for dopamine transporter ligands. Another group of animals, used as controls, was injected with vehicle. After they have reached the required level of striatal dopamine denervation, spinal taps and serum draw were performed before the animals were sacrificed and the brain tissue will be used for proteomics measurements. The results of these monkey studies will be compared with those gathered from serum and CSF measurements collected from at risk patients. Together, these findings could provide the first evidence for the characterization of biomarkers that could predict the development of Parkinson's disease in humans.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 帕金森氏病是一种进行性神经退行性疾病，在首次出现运动症状之前多年就开始了。因此，如果能够在疾病过程的早期进行干预，以减缓或逆转中脑多巴胺能神经元的进行性变性，则可能对疾病的发展产生重大影响。该项目的目标是确定临床前生物标志物，这些生物标志物将有机会用神经保护性治疗药物对高危患者进行预治疗，这可以显着延迟甚至预防多巴胺能神经元的死亡和运动缺陷的发展。与华盛顿大学的Jing Zhang博士合作，该项目旨在使用蛋白质组学方法从MPTP治疗的猴子的血清，脑脊液和脑组织中鉴定此类生物标志物。尽管在该项目中尚未收集到数据，但总共10只猴子已经用MPTP治疗，直到它们达到约30-40%（“无症状组”）或70-80%（“有症状组”）纹状体多巴胺损失，如使用多巴胺转运蛋白配体的PET扫描成像所测量的。 另一组动物用作对照，注射溶剂。在它们达到所需的纹状体多巴胺去神经支配水平后，在处死动物之前进行脊髓穿刺和血清抽取，脑组织将用于蛋白质组学测量。将这些猴研究的结果与从风险患者中采集的血清和CSF测量结果进行比较。总之，这些发现可以为生物标志物的表征提供第一个证据，这些生物标志物可以预测人类帕金森病的发展。