The Role of CK2 in the Development of Levodopa-Induced Dyskinesia in Parkinson’s disease

Promising Outcomes of Original Grant:
In Parkinson’s disease, dopamine-producing neurons degenerate, leading to a lack of dopamine in the brain. This leads to profound changes in the cells which are geared to respond to the dopamine. We have found that a protein, CK2, modulates the efficiency of dopamine signaling. We generated a pre-clinical model where CK2 is deleted in dopamine responsive neurons and found that dopamine signaling in these knockout pre-clinical models was altered. The first grant aimed to investigate whether the lack of CK2 also changed the responses of a pre-clinical model of Parkinson’s disease to levodopa, the major dopamine-replacement therapy. We have found that the genetically modified pre-clinical models have an altered onset of levodopa induced dyskinesia, a major side effect that occurs after chronic levodopa administration.

Objectives for Supplemental Investigation:
We want to understand, on a molecular level, what happens in the genetically modified pre-clinical model after chronic levodopa treatment, and will test whether certain proteins that have previously been linked to the development of levodopa induced dyskinesia are changed.  We will also investigate whether a novel drug which acts on the kinase CK2 has a similar effect on the onset of levodopa induced dyskinesia than the knockout pre-clinical model. We will work with a Parkinson’s disease pre-clinical model that has been widely studied in the context of levodopa induced dyskinesia. We will develop a protocol of administration of the novel drug to the affected brain areas and will observe the development of levodopa induced dyskinesia in these pre-clinical models.

Importance of This Research for the Development of a New PD Therapy:
If our work in pre-clinical models, using the new inhibitor, confirm the results obtained with the pre-clinical model, this could signify that in combination with levodopa this new treatment may delay the onset or the severity of levodopa induced dyskinesia.