Rapid Eye Movement (REM) sleep behavior disorder (RBD) is a sleep disorder characterized by acting out of dreams. Older individuals with RBD frequently develop Parkinson Disease (PD), Dementia with Lewy Bodies (DLB), or Multiple System atrophy (MSA)?collectively termed synucleinopathies?within several years, indicating that RBD is a signal that one of these neurodegenerative diseases has taken root. RBD represents a preclinical stage of synucleionopathy, when brain changes are present but neurodegenerative symptoms have not yet appeared. Subsequently, RBD offers an opportunity to test potential treatments for synucleinopathy at the earliest stages of disease when treatment is most likely to be effective. Based on current information about treatments in the pipeline for synucleinopathies, we anticipate a clinical trial in RBD to protect against synucleinopathy in 2-3 years. However, several gaps prohibit proceeding with a clinical trial currently, including 1) lack of coordination between sites that follow relatively small cohorts, 2) no biomarkers for synucleinopathy, 3) lack of standardization of clinical assessment across sites, 4) 5) lack of a coordinated effort to direct and specifically plan for a neuroprotective clinical trial. To address these gaps, we propose to form the North American Preclinical Synucleinopathy (NAPS) Consortium.
The aims are to form a joint registry of RBD patients, establish standardized assessments and biomarker collection across sites, and institute an expert panel to guide decisions for the NAPS Consortium toward a clinical trial. Through these aims, the NAPS Consortium will build the framework necessary for a successful clinical trial in RBD, including a large and ready patient cohort, standardized functional and biofluid markers, ability to easily scale to new sites, and a clear organizational structure to co-ordinate a multi-site study. The ultimately goal is a successful trial in RBD that can be extended to the general population, to identify and stop PD, DLB, and MSA before any symptoms appear.

Public Health Relevance

Synucleinopathies such as Parkinson Disease, Dementia with Lewy Bodies, or Multiple System Atrophy are frequently preceded by Rapid Eye Movement (REM) sleep behavior disorder (RBD), a sleep disorder characterized by acting out of dreams. The RBD population represents a unique and rich opportunity to find treatments to slow the progression of synucleinopathies, even before people have symptoms. We propose to form the North American Preclinical Synucleinopathy (NAPS) Consortium to enable successful clinical trials for treatments against synucleinopathies, not only for RBD patients, but to reduce the burden of these age-related neurodegenerative diseases in the general population.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Planning Grant (R34)
Project #
3R34AG056639-02S1
Application #
9991500
Study Section
Neuroscience of Aging Review Committee (NIA)
Program Officer
Mackiewicz, Miroslaw
Project Start
2018-05-01
Project End
2021-04-30
Budget Start
2019-09-01
Budget End
2021-04-30
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Washington University
Department
Neurology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130