In previous research, we demonstrated that the protein tumor necrosis factor receptor 2 (TNFR2) plays an essential role in reducing inflammation in the peripheral and central nervous systems. The peripheral nervous system 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, while the central nervous system consists of the brain and spinal cord. We also demonstrated that TNFR2 plays important role in preventing nerve cell death using different cellular and mouse models of neurodegenerative diseases, which affect nerve cells in the brain. The goal of this proposal is to determine if TNFR2 promotes protection of the nervous system in a pre-clinical model of Parkinson's disease.
Selective stimulation of TNFR2 in cells of the brain reduces Parkinsonian signs and modifies the damage to the nervous system seen in a pre-clinical model of Parkinson’s.
We will determine the activity of TNFR2, and whether it is altered throughout the course of the disease. Then, we will evaluate the therapeutic effect after local and whole-body application of an experimental drug that blocksTNFR2. Finally, we will generate novel mice with Parkinson’s that lack TNFR2 activity to evaluate the impact of TNFR2 activity on disease progression.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
This study could identify a new disease-modifying therapy for Parkinson’s that not only reduces disease progression but may also promote regeneration of nerve cells.
Next Steps for Development:
If the present study successfully validates the role of TNFR2 in protecting nerve cells in Parkinson’s, we will perform further studies to better understand the molecular mechanisms. Further, we will develop the experimental TNFR2-blocking drug into a clinical product with the goal to ultimately evaluate the lead candidate in a novel human clinical trial.