Study Rationale:
There are no therapies that slow down the loss of brain cells affected by Parkinson's disease. Prior research suggests that dual leucine zipper kinase (DLK) regulates stress response in brain cells and contributes to cell degeneration and death. Inhibiting DLK may block this response, keep brain cells from dying, and preserve function in people with Parkinson's disease. This pre-clinical study will determine if our drug candidate is suitable for human clinical trials.
Hypothesis:
We hypothesize that our drug candidate, IACS-8287, will slow the death of dopamine-releasing brain cells in a preclinical model of Parkinson's and thus preserve their motor coordination.
Study Design:
We will begin by confirming that DLK, which triggers cell death, is overactive in the brains of Parkinson's patients. Our laboratory work will also determine if our drug can prevent brain cells from dying after exposure to toxic forms of alpha-synuclein protein, which are a hallmark of Parkinson's. If these studies confirm our hypotheses, we will test our drug candidate in pre-clinical models with alpha-synuclein and measure brain cell loss and motor dysfunction to determine if we slowed disease progression. We will also test the drug in early and established disease points, to determine its effectiveness for patients at different stages of Parkinson's.
Impact on Diagnosis/Treatment of Parkinson's disease:
If our hypothesis is true and proven in human patients, then people with Parkinson's could be given this medicine to slow the progression of the disease.
Next Steps for Development:
If this preclinical study is successful, we plan to move our drug candidate to Phase I clinical trials later this year and eventually test it in Parkinson's patients.