Natural Killer Cells Stop Parkinson’s Disease Progression

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Researchers at the University of Georgia’s Regenerative Bioscience Center have discovered that immune cells within the brain can help slow the spread of Parkinson’s by reducing cellular inflammation and clearing protein clumps.  This behavior of “natural killer” white blood cells can guard against the cascade of cellular changes that lead to Parkinson’s disease and help stop its progression.

Natural killer (NK) cells are white blood cells capable of independently killing tumor cells without signaling from the rest of the body. NK cells provide the first line of defense against bacterial or viral invasion and are equipped with activating receptors that can sense cellular stress and identify cells that have been altered due to infection.

“Right now there’s no available therapy to modify or stop the progression of Parkinson’s,” said lead author Jae-Kyung “Jamise” Lee, assistant professor in UGA’s College of Veterinary Medicine. “This would be the first NK study to show the possibility of actually stopping the disease.”

The new study published in the current issue of Proceedings of the National Academy of Sciences, highlights the fact that NK cells act not only as efficient scavengers that attack any non-self intruder, but they may also be critical in regulating and restraining inflammation of brain tissue and the production of protein clumping—hallmarks of Parkinson’s and other neurodegenerative disorders. This study also reported NK cell depletion in a mouse model significantly exaggerated the disease condition.  This led to the researchers to conclude that without NK cells, the nervous system is vulnerable to attack.

“We believe that NK cells exert protection by their ability to reduce inflammation in the brain and clear proteins that misfold and create toxic clumps,” Lee said. “In their absence, proteins were left unchecked, and we saw a substantial decrease in viral resistant cells, confirming that NK cells are a major source of signaling proteins that boost the immune system response.”

Thirty years ago, when research into immunotherapies began, the logical first step was to train the immune system to recognize and attack tumor cells. Today, this idea has successfully moved beyond lab theory: new immunotherapies for melanoma, lung cancer and kidney cancer were recently approved by the U.S. Food and Drug Administration.

Lee is quick to caution that her Parkinson’s work is in animal models, but she is also optimistic about the potential of translating this research into humans. She cited recent human trials that tested immunotherapies against an aggressive form of brain cancer called glioblastoma, indicating that NK cells contribute to elimination of tumor cells.

Parkinson’s is no longer considered a brain-specific disease, and researchers increasingly recognize a functional connection between the immune system and central nervous system. Lee’s team discovered that in conditions of chronic inflammation such as Parkinson’s, the blood-brain barrier becomes disrupted, allowing immune cells to channel into the brain.

“Understanding how the periphery signals for NKs to patrol for infectious agents, even in the absence of disease, could lead to breakthrough treatments for Parkinson’s disease,” Lee said.

Collaborating with Lee on this study is Levi Wood, an assistant professor in Georgia Tech’s School of Mechanical Engineering. The initial partnership between the researchers began with seed funding from the Regenerative Engineering and Medicine (REM) network, a joint collaboration between Emory University, Georgia Tech and UGA. As a REM awardee, Lee leveraged her seed funding into significant support from other groups, including the largest funder of Parkinson’s disease in the world, the Michael J. Fox Foundation.

UGA’s co-director for REM is Steven Stice, who also is director of the RBC.

“REM’s support for high-risk research has provided Dr. Lee the opportunity to rapidly produce some surprising discoveries with tangible results, leveraging the capabilities of a world-renowned, private-sector partner,” said Stice, a Georgia Research Alliance Eminent Scholar in the College of Agricultural and Environmental Sciences. “We are proud to continue to support early-career faculty with bold ideas and big impacts that are solving problems that save lives.”

Initially, the researchers have focused on the neuroprotective effects of NK cells. The next step is to study how NK cell functions are impaired by aging.

“Our preliminary data suggest that the number and function of NK cells are decreased in aged animals, and display impaired ability to perform their normal functions,” Lee said. “We would like to look deeper at age-related changes associated with NK cell biology and the wider implications for the health and well-being of older adults.”

In January, Georgia Gov. Brian Kemp announced that UGA will launch a professorship in honor of former Sen. Johnny Isakson to help develop treatments for Parkinson’s—the same disease that forced the senator to retire from public service. In 2017, Isakson received the Fox Foundation’s Parkinson’s Advocacy Award for his work to improve the lives of people living with the disease and for his advocacy in funding new treatments.

“We are excited to be part of UGA’s community research interest in Parkinson’s and their continued commitment to search for better treatments and a cure,” said Lee.

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