Project: Predicting Phenoconversion

项目：预测表型转化

• 批准号: 10674060
• 负责人: Ronald Postuma
• 金额: $ 14.71万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10674060
• 关键词: Acting Out; Address; Alzheimer' s Disease; Alzheimer' s disease related dementia; American; Antibodies; Behavior; Biological Markers; Blood; Clinical; Clinical Markers; Clinical Research; Clinical Trials; Data; Deposition; Diagnosis; Disease; Dreams; Early Intervention; General Population; Goals; Grant; Individual; Knowledge; LRRK2 gene; Lewy Body Dementia; Logic; Measures; Muscle; Napping; National Institute of Neurological Disorders and Stroke; Neurodegenerative Disorders; Onset of illness; Paralysed; Parkinson Disease; Participant; Patient Selection; Patients; Persons; Pharmaceutical Preparations; Phase; Phase III Clinical Trials; Phenotype; Polysomnography; Population; Process; REM Sleep; REM Sleep Behavior Disorder; Recommendation; Recurrence; Research Personnel; Research Priority; Sample Size; Sampling; Scanning; Selection Criteria; Standardization; Symptoms; Testing; Time; clinical biomarkers; cohort; gene therapy; improved; mitochondrial dysfunction; neuroimaging; neuroinflammation; neuroprotection; phase II trial; preclinical study; predictive marker; prevent; primary outcome; progression marker; prospective; synuclein; synucleinopathy; trial planning

ABSTRACT: NAPS2 PROJECT – PREDICTING PHENOCONVERSION Rapid eye movement (REM) sleep behavior disorder RBD is a condition in which the muscular paralysis that accompanies REM sleep is lost, resulting in recurrent dream enactment behavior. RBD occurs in approximately 40% of patients with PD, 75% of DLB, and 80% of MSA. Idiopathic/Isolated RBD (i.e. without a known associated neurodegenerative disease) occurs in 1% of the population over 50. Landmark studies have suggested that >80% of individuals with this form of RBD in fact have prodromal synucleinopathy, and 6-10% will phenoconvert to PD, DLB, or MSA each year. RBD therefore represents an unprecedented opportunity to directly study early stages of PD, DLB and MSA in detail. Recognizing the importance of early intervention, the key federal agencies focused on neurodegenerative disease in the US have proposed high priority recommendations to study the preclinical and prodromal aspects of synucleinopathies to prepare for clinical trials. The North American Prodromal Synucleinopathy Consortium, Stage 2 (NAPS2) represents expanded and extended efforts of the original NAPS Consortium focused on RBD which began in 2018. In NAPS2, over 300 participants with RBD along with a subset of matched controls will be evaluated in a comprehensive and standardized manner, with the RBD participants undergoing longitudinal clinical, blood and CSF, polysomnographic, and neuroimaging studies. These data, samples and scans will be collected, processed and analyzed in the Cores to provide key variables for conducting hypothesis-driven analyses in the Project, with the focus on Predicting Phenoconversion. This project will therefore seek to address many critical scientific issues pertaining to RBD and neuroprotective clinical trial planning, including the following: 1) determining the degree and distribution of abnormalities in clinical measures, PSG and biofluid biomarkers among a large cohort of persons with RBD; 2) determining the conversion rate from RBD to an overt synucleinopathy, and to define predictive biomarkers of phenoconversion; 3) tracking change on clinical measures and biomarkers to develop progression biomarkers of synucleinopathy, and 4) combining data on phenoconversion, predictive biomarkers, and progression biomarkers to estimate sample size according to different patient selection criteria and primary outcomes for neuroprotective clinical trials in RBD.

摘要：NAPS 2项目-预测现象转化 快速眼动（REM）睡眠行为障碍RBD是一种肌肉麻痹的情况， 伴随着快速眼动睡眠的大脑活动丧失，导致反复的做梦行为。RBD发生在 大约40%的PD患者、75%的DLB患者和80%的MSA患者。特发性/孤立性RBD（即无 已知相关的神经变性疾病）发生在50岁以上人群的1%中。项里程碑研究 事实上，超过80%的RBD患者患有前驱期突触核蛋白病，6-10%的RBD患者患有前驱期突触核蛋白病。 每年都会转化为PD、DLB或MSA。因此，RBD代表了一个前所未有的机会， 直接详细研究PD、DLB和MSA的早期阶段。认识到早期干预的重要性， 在美国，专注于神经退行性疾病的主要联邦机构已经提出了高度优先考虑的建议， 建议研究突触核蛋白病的临床前和前驱方面， 审判北美前驱体突触核蛋白病联盟，第2阶段（NAPS 2）代表 最初的NAPS联盟的扩大和扩展工作集中在2018年开始的RBD。在 NAPS 2中，将对300多名RBD沿着受试者以及匹配对照组的一个子集进行评价， 全面和标准化的方式，与RBD参与者进行纵向临床，血液和 CSF、多导睡眠图和神经影像学研究。这些数据、样本和扫描将被收集， 在核心中进行处理和分析，以提供关键变量， 项目，重点是预测表型转化。因此，该项目将寻求解决许多 与RBD和神经保护临床试验计划有关的关键科学问题，包括以下内容：1） 确定临床测量、PSG和生物流体生物标志物中异常的程度和分布 在一个大的RBD人群中; 2）确定从RBD到显性RBD的转化率， 突触核蛋白病，并定义表型转换的预测性生物标志物; 3）跟踪临床 用于开发突触核蛋白病的进展生物标志物的措施和生物标志物，以及4）组合关于以下的数据： 表型转化、预测性生物标志物和进展生物标志物，以根据 不同的患者选择标准和RBD神经保护临床试验的主要结局。