Long before they exhibit the classical symptoms of Parkinson’s disease—tremor, slowness of movement, impairment of gait and balance, and cognitive decline—nearly half of all future Parkinson’s patients experience a seemingly unrelated symptom: restless sleep.

Instead of slumbering peacefully, these patients physically act out their dreams, often vocalizing and violently moving their arms and legs during deep sleep. Called REM Sleep Behavioral Disorder, the syndrome emerges when the mechanisms in the brain that normally freeze the motor systems begin to fail.

While the relationship between this sleep disorder and neurodegenerative illness is not yet clear, research indicates that it may be an early marker or predictor, often appearing years or even decades before the typical symptoms of Parkinson’s.

More than half of those who develop REM Sleep Behavioral Disorder will, within the next decade, go on to develop Parkinson’s motor symptoms such as tremor, rigidity, slowed movement, and difficulty walking. Over time, patients with the sleep disorder also accumulate non-motor symptoms such as cognitive changes, depression, and anxiety. Patients’ brains also begin to appear more like those of Parkinson’s patients on neural imaging, meaning that REM Sleep Behavioral Disorder can be categorized as a “prodromal” syndrome presaging the development of clinically evident Parkinson’s.

A New Angle for Treatment

David Hafler, MD, chair of the Department of Neurology and William S. and Lois Stiles Edgerly Professor of Neurology and of Immunobiology, along with neurology professor Jesse Cedarbaum, MD, has been researching the relationship between the sleep disorder and neurodegenerative illness, and they have discovered a potential key that could unlock a new type of Parkinson’s treatment.

In their research, Hafler and Cedarbaum found inflammation in the spinal fluid of individuals with REM Sleep Behavioral Disorder, leading them to theorize that inflammatory signaling plays a key role in Parkinson’s development. The researchers hypothesize that blocking these signals could delay or prevent the onset of Parkinson’s. Such therapy might just be the answer Parkinson’s researchers have been looking for.

Current treatments of Parkinson’s all focus on slowing the disease’s progression or managing its symptoms, but this new strategy could stop the symptoms before they even begin.

Testing the Theory

Thanks to a grant from The Marcus Foundation, this theory can be put to the test. The gift will fund a clinical trial in people with REM Sleep Behavioral Disorder. The trial will use adalimumab—also known as Humira®—an FDA-approved anti-inflammatory medication used to treat autoimmune disorders, to attempt to prevent the development of Parkinson’s. This trial represents the first large-scale effort of this type.

“We are thrilled that, thanks to The Marcus Foundation, we can test a readily available treatment that holds the potential to change the standard of care for Parkinson’s disease,” Hafler says. “If successful, this trial stands to benefit immediately the lives of patients and families facing devastating diagnoses.”

The Marcus Foundation, chaired by Bernie Marcus, co-founder and former chairman and CEO of the Home Depot, provides targeted and impactful philanthropy in the areas of medical research, free enterprise and veterans support, Jewish causes, and the community.

“We are grateful to The Marcus Foundation for its generosity and commitment to supporting our innovative translational research in neuroscience, especially on the pathogenesis and treatment of neurodegenerative conditions such as Parkinson’s disease,” says Nancy J. Brown ‘81, MD, the Jean and David W. Wallace Dean of Yale School of Medicine. “The clinical impact of the study could potentially help patients by preventing emergence of the debilitating motor and cognitive symptoms of Parkinson’s.”