Inhibition of a Dopamine Receptor in Lymphocytes as a Treatment for Parkinson's Disease
Target Validation, 2014
Objective/Rationale: † † † † † ††
Emerging evidence has shown that lymphocytes, a kind of immune system cells, play a fundamental role in the development and progression of Parkinson's diseases. Our previous study demonstrated that a receptor for dopamine (DR) is pivotal in the detrimental function of lymphocytes in Parkinson's disease. In this project, we will test the therapeutic potential of inhibition of DR in lymphocytes as a treatment for Parkinson's disease.
We will purify lymphocytes from pre-clinical models and inhibit DR using two different techniques: inhibit stimulation of this receptor and inhibition the production of DR by lymphocytes. After inhibition of DR in lymphocyte culture, these cells will be injected in pre-clinical models of Parkinson's disease. We will evaluate recuperation of movement control, neuronal death and inflammatory response in the brain. Moreover, we will also determine whether there is an association between the quantity of DR in lymphocytes and the degree of disease progression and severity of Parkinson's disease.
Relevance to Diagnosis/Treatment of Parkinsonís Disease: † † † † † † † † † ††
This project will allow us to determine whether inhibition of DR specifically in lymphocytes is able to decrease or stop the progression of Parkinson's disease in a model. Thereby, the potential results could give us the clues for the generation of an immunotherapy for human Parkinson's disease. Furthermore, potential results can also give useful information for diagnosis of early Parkinson's disease and for patient's responsiveness to DR-based therapy by detecting changes on DR quantity in blood lymphocytes.
Anticipated Outcome: † † † † †
Our preliminary data shows promising results in which the injection of lymphocytes pre-treated with the specific drug for DR inhibition results in a significant reduction in neuronal death. We expect that the treatment of Parkinson's disease models with lymphocytes in which production of DR has been inhibited will show even stronger therapeutic effects attenuating neuronal death, brain inflammation and movement impairment.
Associate Investigator and Head of the Laboratory of Neuroimmunology at Fundaciůn Ciencia & Vida
Location: Santiago, Chile