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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 帕金森氏病是一种进行性神经退行性疾病，在出现第一次运动症状之前的许多年开始。因此，如果人们可以在疾病过程的早期进行干预，以减慢或扭转中脑多巴胺能神经元的进行性变性，则可能会对疾病的发展产生重大影响。该项目的目的是确定临床前生物标志物，这些临床前生物标志物将有机会预先治疗患有神经保护性治疗药物的患者，这可能会大大延迟甚至可以防止多巴胺能神经元死亡和运动缺陷的发展。该项目与华盛顿大学的Jing Zhang博士合作，旨在使用MPTP处理的猴子中的血清，脑脊液和脑组织中的蛋白质组学方法来识别此类生物标志物。尽管该项目尚未收集数据，但总共使用MPTP处理了10只猴子，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PET扫描的多巴胺转运剂配体测量。 另一组用作对照的动物被注入了媒介物。在他们达到所需水平的纹状体多巴胺神经支配水平后，在处死动物之前先进行脊柱水龙头和血清抽水，并将脑组织用于蛋白质组学测量。这些猴子研究的结果将与从风险患者收集的血清和CSF测量结果中收集的结果进行比较。这些发现共同提供了可以预测人类帕金森氏病发展的生物标志物表征的第一个证据。