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

大多数患有快速眼动(REM)睡眠行为障碍(RBD)的人会出现额外的神经系统症状，随后被诊断为明显的联核病，包括路易体痴呆(DLB)、帕金森病(PD)和多系统萎缩(MSA)，这表明RBD是联核病的前驱阶段。因此，RBD提供了在疾病最有可能有效的早期阶段进行神经保护治疗干预的机会之窗。认识到早期干预的重要性，专注于神经退行性疾病的主要联邦机构已经就联核疾病的前驱方面提出了高度优先的建议，特别是RBD，以准备临床试验。北美前驱综合征(NAP)联盟于2018年开始计划RBD的神经保护临床试验。NAPS联盟目前在10个地点，到目前为止已经招募了215名患有多导睡眠图确认的RBD的参与者，并成功地进行了全面和标准化的评估和生物液收集。北美RBD先兆综合征第二阶段(NAPS2)计划代表着NAPS的综合扩展，以支持RBD的纵向、前瞻性研究，以解决目前阻碍RBD神经保护性临床试验的关键空白。NAPS2将建立增强的基础设施，以支持前驱联体核病的长期研究。我们将建立8个核心-行政、临床、生物流体、神经成像、多导睡眠图(PSG)、遗传学、数据管理和统计(DMS)以及招募、教育和外展(REO)-以增强我们的方案并支持一个预测表型转化为显性突触核病的项目。NAPS2将前瞻性地评估&gt；300名RBD患者，进行全面的临床评估和收集PSG/神经生理学、生物流体(血液和脑脊液)、遗传和神经成像(MRI和DaTcan)生物标记物。NAPS的首要目标是使神经保护性临床试验能够预防或推迟突触核病。为了实现这一目标，NAPS2的目标是：1)研究RBD作为DLB、PD和MSA的前驱表现；2)扩大RBD参与者的队列，增加匹配的对照参与者，以纵向、标准化地收集临床、PSG、遗传、生物流体和神经成像数据；3)对照纵向临床结果分析收集的数据，以改进量表和开发生物标记物，以优化临床试验；4)共享供科学界使用的数据、样本和方法；5)与NIH、其他RBD科学团体、行业合作伙伴、患者和其他团体互动；6)为大规模临床试验做准备。最终，在RBD人群中开发的联核病生物标志物和神经保护性治疗可以应用于更大的联核病风险人群，以延迟或预防DLB、PD和MSA。

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.