Study Rationale:
Parkinson's disease (PD) involves accumulation of toxic proteins in cells in specific areas of the brain. These cells normally have protective mechanisms to remove these toxic proteins and dysfunction of these mechanisms may play a role in the development of PD. A major goal of this grant is to explore novel ways to allow these cells to restore their ability to remove these toxic proteins.
Hypothesis:
Key members of the deubiquitinase (DUB) family of enzymes are thought to play a central role in the development and progression of PD by allowing the build-up of toxic proteins. This study will determine if inhibitors of these enzymes can prevent or halt the progression of PD.
Study Design:
The grant recipients have expertise in the identification of drugs that block the action of DUBs. The team will apply this expertise to DUB family members that are thought to play a central role in the development and progression of PD to find new drugs. Once candidate drugs are identified, the team will work closely with MJFF scientists to verify that these drugs have the expected potential to modify PD.
Impact on Diagnosis/Treatment of Parkinson's Disease:
There are no current therapies for PD that target the elimination of toxic proteins that can lead to PD. Oral DUB inhibitors could potentially benefit those with PD by addressing symptoms or slowing progression of the disease.
Next Steps for Development:
The overall goal of this work is to find drug candidates that enter the brain and stop the progression of PD in pre-clinical models of the disease. The best drug candidate will be evaluated pre-clinically for safety and subsequently enter clinical trials. Ultimately, we aim to deliver a safe and efficacious DUB inhibitor that would improve quality of life for those with Parkinson's and their families.