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

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.