Objective/Rationale:
Evidence in humans and in research models support a role for the immune system in the progression of Parkinson's disease. Our preliminary data suggest infiltration of peripheral immune cells expressing the CD163 receptor selectively into the area of neurodegeneration in different PD models. We hypothesized that the selective migration of peripheral macrophages into the injured area suggests a role for macrophages in the disease progression that may influence local immune cells in the area of neurodegeneration.
Project Description:
In this project we will characterize the CD163 expression in Parkinson’s disease both in human post-mortem tissue and in pre-clinical models of the disease. In addition we will address whether the CD163 expressing macrophages can be used a tools to deliver drugs into brain in pre-clinical models to modify local immune response to the neurodegeneration with the aim of achieving neuroprotection. To do so we will use nanoparticles targeted specifically to deliver anti-inflammatory drugs into cells that express the receptor CD163.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Our ultimate goal in this project is to determine whether modulation of inflammation by targeting a specific population of peripheral macrophages is a putative novel therapy in PD. The possibility of modulating brain response by aiming peripheral/blood cells will open wide possibilities for neurprotective approaches in humans.
Anticipated Outcome:
We anticipate that our experiments will validate the use of the receptor CD163 for nanoparticles targeting in Parkinson’s disease. If confirmed its efficiency it will open possibilities of approaching this receptor to target macrophages with different compounds. This will allow us to address the ability of new potential drugs or strategies to modulate the disease via macrophages in the future.
Final Outcome
Our data suggest a neuroprotective role for the CD163 targeted anti-inflammatory therapy in Parkinson’s disease aimed to modulate immune response during the neurodegenerative process. Pre-clinical models subjected to a neurotoxic model of Parkinson’s disease that received this therapy showed improved motor behavior and increased number of surviving neurons in the substantia nigra. The data obtained so far, encourage us to further approach this therapy in an alpha-synuclein based Parkinson’s model. The possibility of treating the brain by targeting peripheral cells is a very attractive approach for clinical use that we will further investigated. We believe these and other future findings can be applied to other neurodegenerative disorders with neuroinfalmmation.