$ 35 million in assist of Sleep Disorders-Associated Neurodegeneration Study – Washington University School of Medicine, St. Louis

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International team searches for hidden of brain damage in REM behavior disorder

One study participant wears monitoring devices as part of a sleep study on REM sleep behavior disorder. Researchers at Washington University School of Medicine in St. Louis, Mayo Clinic in Rochester, Minnesota, and The Neuro (Montreal Neurological Institute-Hospital) at McGill University have a five-year grant, estimated to be 35.1 million, to study biomarkers , which show which people with the sleep disorder will later develop neurodegenerative diseases.

“data-medium-file =” https://medicine.wustl.edu/wp-content/uploads/202100520_NAPS_0118_forweb-300×200.jpg “data-large-file =” https://medicine.wustl.edu/wp-content /uploads/202100520_NAPS_0118_forweb-700×467.jpg “/>Matt Miller

People with Rapid Eye Movement (REM) sleep behavior disorder are living out their dreams. For example, while sleeping safely in bed, they can raise their arms to catch an imaginary ball or try to run away from an illusory attacker. Such actions are more than just a nuisance. People with this disorder have a 50 to 80% chance of developing severe neurodegenerative disease within a decade of being diagnosed.

An international team led by researchers from Washington University School of Medicine in St. Louis, Mayo Clinic in Rochester, Minnesota, and The Neuro (Montreal Neurological Institute-Hospital) of McGill University has a five-year scholarship estimated to be 35, US $ 1 million will be given to develop biomarkers that show which people with the sleep disorder will later develop neurodegenerative diseases, what specific diseases will occur, when symptoms will appear, and how quickly the diseases will progress. This grant – from the National Institute on Aging (NIA) and the National Institute of Neurological Disorders and Stroke (NINDS), both National Institutes of Health (NIH) – will help lay the foundation for clinical trials that focus on to stop the annoying disease from progressing to a debilitating disease.

“The likelihood of people with REM sleep behavior disorder developing neurodegenerative disease is pretty alarming, and there are currently no treatments to reduce that risk,” said Yo-El Ju, MD, neurologist and co-research director at Washington University. “We have no way of predicting whether and how quickly someone will develop one of these diseases or which ones they will get. And we certainly don’t know how we can prevent that. “

REM sleep behavior disorder is linked to Parkinson’s disease, a state of movement; Dementia with Lewy bodies that causes cognitive decline; and multiple system atrophy, in which the ability to regulate involuntary functions such as blood pressure, breathing, and bladder and bowel function deteriorates.

Usually people are paralyzed in REM sleep, the phase of sleep in which dreaming takes place. Acting out dreams is an early sign that something in the brain is not working as it should. REM sleep behavior disorder is linked to diseases caused by abnormal clumps of the protein alpha-synuclein in the brain. Such lumps often condense early in the course of the disease in a part of the brain that paralyzes the body during REM sleep. When this area becomes damaged, people start beating around while dreaming.

Several drugs and immunotherapies targeting alpha-synuclein are currently being developed and may be available for clinical trials in REM sleep behavior disorders. But first, the scientists need to identify a series of results on specific tests or biomarkers for impending neurological diseases in people with REM sleep behavior disorder.

“Information predicting the timing and type of synucleinopathy disorder is almost certainly hidden in one or more of the biomarkers being evaluated in this study,” said Bradley Boeve, MD, a neurologist with the Mayo Clinic and co- Research director of the scholarship. “If we can identify biomarkers that predict the future, we can focus on those biomarkers for upcoming clinical trials that should delay or prevent the onset of dementia or parkinsonism.”

Boeve, The Little Family Foundation Professor of Lewy Body Dementia at Mayo Clinic, and Ju, Barbara Burton and Reuben Morriss III Professor of Neurology at Washington University, founded the North American Prodromal Synucleinopathic (NAPS) Consortium in 2018 to help a group of people with REM sleep behavior disorder and develop standardized tools to investigate them. More than 350 people with REM sleep behavior disorder have enrolled in the NAPS consortium. The new grant funds a larger study aimed at identifying biomarkers in these individuals as well as new participants.

This larger study, named NAPS2, is being led by Ju, Boeve, and co-lead investigator Ronald Postuma, MD, of The Neuro and the Research Institute of the McGill University Health Center. This study will follow approximately 430 participants with REM sleep behavior disorder and 60 people without sleep problems for five years. Patients and control subjects are regularly subjected to extensive clinical examinations and overnight sleep studies. They will also provide blood samples and, if requested, cerebrospinal fluid. Participants with REM sleep behavior disorder will also have brain scans.

“NAPS2 is another example of the coordinated and collaborative support the NIH provides to advance the discovery and understanding of devastating brain diseases,” said Mack Mackiewicz, PhD, program director in the NIA Division of Neuroscience and NIA project scientist at the Scholarship. “This project, which looks at sleep as a risk factor for dementia, is just one example of the broad spectrum of research the NIH is promoting on neurodegenerative diseases.”

NIA and NINDS fund NAPS2 equally with joint scientific contributions and NIA oversees the project.

More than 2 million people in the United States are living with Lewy Body Disorder, a group of diseases caused by alpha-synuclein clots in their brain. These so-called synucleinopathies include dementia with Lewy bodies, Parkinson’s disease and multiple system atrophy. Taken together, they are the second most common neurodegenerative disease after Alzheimer’s disease.

Alzheimer’s disease and synucleinopathies have several things in common. In both of these, abnormal clumps of protein build up in the brain for years before symptoms appear: amyloid and tau in Alzheimer’s disease and synuclein in Lewy body diseases. About half of people with Alzheimer’s-related amyloid and tau lumps also have synuclein lumps, which is why synucleinopathies are classified as Alzheimer’s-related dementias. In addition, symptoms such as changes in thinking and behavior occur early in the course of the disease in both diseases.

Not all people with Lewy Body Disorder will have movement problems while sleeping before the onset of neurological symptoms. But studying people with REM sleep behavior disorder in the earliest stages of a neurodegenerative process can shed light on how abnormal clumps of protein cause brain damage, how various symptoms appear, and how the neurodegenerative process can be stopped or slowed down.

“The main goal of this research is to find ways to reliably identify early Parkinson’s disease, Lewy body dementia and multiple system atrophy,” said Postuma. “When we do this, we can start planning disease prevention studies. So far we have very good clinical predictors for disease, but biomarker research is still catching up. Biomarkers are important to determine exactly what stage of the disease people are in so that more targeted therapies can be offered. “

Nine clinical centers are participating in the study: Emory University, Massachusetts General Hospital / Harvard School, Mayo Clinic, McGill University Health Center Research Institute, Stanford Medicine, UCLA, University of Minnesota, Veterans Affairs Portland / Oregon Health Sciences University, and Washington University .

This study is supported by the National Institute on Aging and the National Institute of Neurological Disorders and Stroke of the two US National Institutes of Health (NIH) under grant number U19AG071754. This grant represents 100% of the total cost of the program. The authors are solely responsible for the content and do not necessarily represent the official views of the NIH.

The 1,700 faculty physicians at Washington University School of Medicine are also the staff for the Barnes-Jewish and St. Louis Children’s Hospitals. The School of Medicine is a leader in research, teaching, and patient care and consistently ranks among the top schools in the country according to the US News & World Report. The School of Medicine is affiliated with BJC HealthCare through its affiliation with Barnes-Jewish and St. Louis Children’s Hospital.

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