CD163+ Macrophages as Tools for Neuroinflammatory Modulation in Parkinson’s Disease Supplement

Promising Outcomes of Original Grant:
Our fundamental hypothesis was that modulation of blood CD163+ macrophages using nanoparticles loaded with anti-inflammatory drugs could protect neurons in the brain of models of Parkinson’s disease. Indeed, when we used such an approach, less neurons died after a neurotoxin injection into the model brain, and the animals exhibited less motor defects related to the brain lesion. Furthermore, the use of targeted nanoparticles allowed us to minimize the dose of the anti-inflammatory drug, which reduced the side effects commonly observed with higher therapeutic doses.

Objectives for Supplemental Investigation:           
Our data supports a role for the CD163 macrophagic population in the disease progression. Therefore, in this experiment, we will further characterize the cells that we have targeted using both human samples and models of the disease. We will analyze the status of the CD163 macrophagic population during the disease in order to gain knowledge important for designing our future therapeutic strategy. In parallel we will deplete the macrophagic CD163 population in models to analyze their role during dopaminergic neurodegeneration. Finally, we will further test the neuroprotective potential of our approach in an alpha-synuclein based model of Parkinson’s disease. 

Importance of This Research for the Development of a New PD Therapy:      
The possibility of targeting a subpopulation of peripheral cells in blood that can travel to brain and exert their neuroprotective role in the area of degeneration opens possibilities. This research may lead to design of novel nanoparticles loaded with drugs that can more elegantly and specifically help the neurons in brain while avoiding toxicity.