In Parkinson’s disease, brain cells die when their mitochondria (structures that create energy for the cells) are damaged and cannot be removed efficiently. An enzyme called parkin helps to remove these damaged cell structures. Drugs that increase parkin activity in the brain have the potential to preserve brain cells and thereby stop Parkinson’s disease from progressing.
A small molecule activator of parkin, discovered in the first part of this project, will be evaluated to determine whether it can be improved by changing its chemical structure so that it can be given to experimental animals and remain in the body long enough to be an effective drug.
We will make new compounds by modifying the structure of our parkin activator P0063409 to make them stronger, more soluble, and better able to work in the body and especially to enter the brain to rescue the dying brain cells. These improved molecules will be tested in biochemical experiments, in cells, and in whole animals to see which will be the best candidates for clinical development. These compounds will be chosen for the next phase, in which they will be tested in animals to determine whether they have the potential to reverse Parkinson’s disease in human clinical trials.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
The goal of the project is to develop a drug that will be approved for stopping the advance of Parkinson’s disease rather than just temporarily treating the symptoms of the disease, as all of the current Parkinson’s drugs do. Any drug that can stop or reverse Parkinson’s disease would be a breakthrough.
Next Steps for Development:
Next, the drug will be tested in animals to see whether it is safe and is able stop the killing of brain cells and the progression of Parkinson’s. Other steps include making large amounts of the drug for clinical trials in humans and applying to the Food and Drug Administration to conduct clinical trials.