Toxic proteins produced in the brains of people with Parkinson's disease (PD) are known to set off an immune response. In the course of this response, inflammatory lymphocytes -- immune cells that promote inflammation -- enter the brain, where they attack and harm brain cells. Of note, pre-clinical models lacking lymphocytes do not develop Parkinson's, indicating that lymphocyte-driven inflammation is necessary for the death of brain cells and progression of the disease. Importantly, immunosuppressive lymphocytes -- another type of immune cells -- deactivate inflammatory lymphocytes and, thus, play the opposite, anti-inflammatory role.
Immunosuppressive lymphocytes directed specifically at toxic proteins in the brain are expected to reduce the effects of inflammatory lymphocytes, including the death of brain cells that underlie Parkinson's disease progression.
Using genetic methods, we will engineer lymphocytes with immunosuppressive activity and with receptors -- sensing molecules -- on their surface that can recognize toxic proteins produced in the brains of people with PD. These engineered lymphocytes will be injected into pre-clinical models with Parkinson's features. We will then measure movement and neurodegeneration in these models to evaluate therapeutic potential of the lymphocytes.
Impact on Diagnosis/Treatment of Parkinson's disease:
This study will test the therapeutic potential of the immunosuppressive lymphocytes equipped with receptors that recognize toxic proteins in the brains of pre-clinical models with Parkinson's features.
Next Steps for Development:
If this experimental therapy is successful in pre-clinical models, we will test its safety in pre-clinical models. Next, we will evaluate its safety and therapeutic potential in individuals with Parkinson's disease.