Promising Outcomes of Original Grant:
Our original study investigated whether immune cells called human natural killer (NK) cells play a protective role on the nervous system in Parkinson’s disease. We evaluated the role of NK cells in a preclinical model with Parkinson’s features. We demonstrated that there were significantly aggravated Parkinson’s features including clumps of a protein called alpha-synuclein in the brain and motor deficits in the absence of NK cells. These suggest a protective role for NK cells in synuclein-related diseases that affect the nervous system. Our study provided evidence of potential usefulness of NK cells as a potential therapeutic for Parkinson’s and Lewy body dementia.
Objectives for Supplemental Investigation:
Our original work has successfully demonstrated the protective role of NK cells on the nervous system in a preclinical model of Parkinson’s. The next steps for the project are to expand our observations to determine if the protective effects of NK cells are also found in the peripheral nervous system. People with Parkinson’s patients have signs of disease in both the central nervous system (brain and spinal cord) and the peripheral nervous system, which includes all of the nerves that branch out from the brain and spinal cord and extend to other parts of the body including muscles and organs.
We will determine whether NK cell depletion affects disease in the peripheral nervous system and development of alpha-synuclein clumps, or aggregates, to further understand the role of NK cells in peripheral tissues. In this supplemental investigation, we will also establish a protocol to characterize NK cells of people with Parkinson’s to see if they different from people without the disease. These studies will enable us to analyze the Parkinson’s-related changes in NK cell subsets or cell receptors that may contribute to disease progression.
Importance of This Research for the Development of a New Parkinson's Therapy:
Utilizing immune cells to stop the spreading of toxic clumps of alpha-synuclein protein and inhibit degeneration of the nervous system may be a promising therapeutic avenue for Parkinson’s and Lewy body dementia. In this study, we will address a novel and paradigm-shifting hypothesis on the role of natural killer cells in the development of synuclein-related disease. This study may lead to novel NK cell mechanisms in age-related neurodegenerative diseases and immune cell target strategies.