Study Rationale:
For over 30 years, scientists have linked lipid oxidation, a type of damage to cellular fats, with Parkinson’s disease. However, the precise cause of this damage remains unknown. This project investigates whether a specific enzyme, 15-lipoxygenase (15-LO), is the culprit. We are using a newly developed drug, CU-13001, to block 15-LO activity in pre-clinical models of Parkinson’s to see if this prevents the brain cell damage associated with the disease.
Hypothesis:
We predict that overactive 15-Lipoxygenase (15-LO) is a primary cause of lipid damage in the brain. We believe this damage triggers the three main hallmarks of Parkinson's: the clumping of alpha-synuclein protein, brain inflammation, and the death of nerve cells.
Study Design:
We will test the protective effects of our drug, CU-13001, in two pre-clinical models that model Parkinson’s disease. Both models develop high levels of sticky alpha-synuclein protein, which leads to inflammation and cell death. The pre-clinical models will receive daily oral doses of CU-13001 for several months. Afterward, we will examine their brain tissue to determine whether the drug successfully reduced inflammation, prevented protein aggregation, and protected nerve cells from dying.
Impact on Diagnosis/Treatment of Parkinson’s disease:
Most current treatments for Parkinson’s only manage symptoms (like tremors) without stopping the disease itself. If our drug works in these studies, it would prove that blocking 15-LO is a viable strategy to actually slow or halt the progression of the disease, offering a new hope for a "disease-modifying" therapy.
Next Steps for Development:
The results from this project are the final piece of the puzzle needed before advancing to human trials. If successful, these data will enable us to finish required safety testing and officially apply for approval to start Phase 1 clinical trials with CU-13001 in people with Parkinson’s disease.