North American Prodromal Synucleinopathy Consortium for RBD, Stage 2 (NAPS2)

北美 RBD 前驱突触核蛋白病联盟，第 2 阶段 (NAPS2)

• 批准号: 10457855
• 负责人: Bradley F Boeve
• 金额: $ 701.63万
• 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 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10457855
• 关键词: Address; Age; Alzheimer' s Disease; Alzheimer' s disease related dementia; American; Basic Science; Biological Assay; Biological Markers; Blood; Cerebrospinal Fluid; Clinical; Clinical Data; Clinical Sciences; Clinical Trials; Clinical Trials Design; Collection; Communities; DNA; Data; Databases; Dementia with Lewy Bodies; Development; Diagnosis; Disease; Early Intervention; Education and Outreach; Enrollment; Future; Genetic; Goals; Individual; Infrastructure; Institutes; Lewy Body Dementia; Longitudinal prospective study; Magnetic Resonance Imaging; Measures; Methods; Motor; Multiple System Atrophy; Napping; Nervous System Physiology; Neurodegenerative Disorders; Neurologic; Neurologic Symptoms; Outcome; Parkinson Disease; Participant; Patients; Phenotype; Plasma; Population; Populations at Risk; Protocols documentation; REM Sleep Behavior Disorder; Race; Recommendation; Registries; Research; Risk; Sampling; Scanning; Screening procedure; Secondary to; Site; Standardization; Structure; Testing; United States National Institutes of Health; Update; central database; cohort; data management; data sharing; industry partner; meetings; multimodal data; nervous system disorder; neuroimaging; neurophysiology; prevent; programs; prospective; recruit; repository; research clinical testing; sex; statistics; synucleinopathy

Most individuals with rapid eye movement (REM) sleep behavior disorder (RBD) develop additional neurological symptoms and are subsequently diagnosed with overt synucleinopathies, including dementia with Lewy bodies (DLB), Parkinson’s disease (PD), and multiple system atrophy (MSA), indicating that RBD represents a prodromal stage of synucleinopathy. RBD therefore offers a window of opportunity to intervene with neuroprotective treatments at the earliest stages of disease when treatment is most likely to be effective. Recognizing the importance of early intervention, key federal agencies focused on neurodegenerative disease have proposed high priority recommendations for prodromal aspects of synucleinopathies, including specifically RBD, to prepare for clinical trials. The North American Prodromal Synucleinopathy (NAPS) Consortium began in 2018 to plan for neuroprotective clinical trials in RBD. The NAPS Consortium, currently at 10 sites, has thus far enrolled 215 participants with polysomnogram-confirmed RBD, and has successfully performed comprehensive and standardized assessments and biofluids collection. The North American Prodromal Synucleinopathy Consortium for RBD, Stage 2 (NAPS2) program represents an integrated expansion of NAPS to support a longitudinal, prospective study of RBD, to address key gaps currently prohibiting neuroprotective clinical trials in RBD. NAPS2 will establish enhanced infrastructure to support long-term research in prodromal synucleinopathies. We will institute 8 Cores—Administrative; Clinical; Biofluid; Neuroimaging; Polysomnogram (PSG); Genetics; Data Management and Statistics (DMS); and Recruitment, Education, and Outreach (REO)—to augment our protocol and to support a Project to predict phenoconversion to overt synucleinopathy. NAPS2 will prospectively assess >300 participants with RBD for comprehensive clinical evaluation and collection of PSG/neurophysiological, biofluid (blood and cerebrospinal fluid), genetic, and neuroimaging (MRI and DaTscan) biomarkers. The overarching goal of NAPS is to enable neuroprotective clinical trials to prevent or delay synucleinopathies. Toward this goal, the NAPS2 aims are: 1) to conduct research on RBD as a prodromal manifestation of DLB, PD, and MSA; 2) to expand our cohort of RBD participants and add matched control participants for longitudinal, standardized collection of clinical, PSG, genetic, biofluid, and neuroimaging data; 3) to analyze collected data against longitudinal clinical outcomes to refine scales and develop biomarkers to optimally design clinical trials; 4) to share data, samples, and methods for use by the scientific community; 5) to interact with NIH, other scientific groups on RBD and overt synucleinopathies, industry partners, patients, and other groups; and 6) to prepare for large-scale clinical trials. Ultimately, synucleinopathy biomarkers and neuroprotective treatments developed in the RBD population could be applied to the larger population at risk for synucleinopathies, to delay or prevent DLB, PD, and MSA.

大多数快速眼动（REM）睡眠行为障碍（RBD）患者会出现额外的神经系统症状，并随后被诊断为明显的突触核蛋白病，包括路易体痴呆（DLB）、帕金森病（PD）和多系统萎缩（MSA），这表明RBD代表了突触核蛋白病的前驱阶段。因此，RBD提供了一个机会窗口，在疾病的早期阶段进行神经保护治疗，此时治疗最有可能有效。认识到早期干预的重要性，重点关注神经退行性疾病的关键联邦机构提出了优先考虑突触核蛋白病（特别是RBD）前驱症状的建议，以准备临床试验。北美前驱突触核病（nap）联盟于2018年开始计划在RBD中进行神经保护临床试验。nap联盟目前在10个地点，迄今已招募了215名患有多导睡眠图证实的RBD的参与者，并成功地进行了全面和标准化的评估和生物体液收集。北美RBD前驱突触核病联盟2期（NAPS2）项目代表了nap的综合扩展，以支持RBD的纵向前瞻性研究，以解决目前禁止RBD神经保护临床试验的关键空白。NAPS2将建立增强的基础设施，以支持前驱突触核蛋白病的长期研究。我们将建立8个核心——行政；临床;Biofluid;神经影像;Polysomnogram (PSG);遗传学;数据管理和统计；招募、教育和推广（REO），以加强我们的方案，并支持一个预测显性突触病表型转化的项目。NAPS2将对bbb300名RBD患者进行前瞻性评估，以进行全面的临床评估和PSG/神经生理、生物液（血液和脑脊液）、遗传和神经影像学（MRI和DaTscan）生物标志物的收集。nap的总体目标是使神经保护临床试验能够预防或延迟突触核蛋白病。为此，NAPS2的目标是：1)将RBD作为DLB、PD和MSA的前驱表现进行研究；2)扩大RBD参与者的队列，并增加匹配的对照参与者，进行临床、PSG、遗传、生物体液和神经影像学数据的纵向、标准化收集；3)根据纵向临床结果分析收集到的数据，以完善量表和开发生物标志物，以优化临床试验设计；4)共享数据、样本和方法，供科学界使用；5)与NIH、其他有关RBD和显性突触核蛋白病的科学团体、行业合作伙伴、患者和其他团体进行互动；6)为大规模临床试验做准备。最终，在RBD人群中开发的突触核蛋白病变生物标志物和神经保护治疗可以应用于有突触核蛋白病变风险的更大人群，以延迟或预防DLB、PD和MSA。