Potential Utility of Novel CNS-active Experimental Therapeutics for Parkinson's Disease

Objective/Rationale:
Evidence suggests that overproduction of inflammatory molecules, called proinflammatory cytokines, from glial cells in the brain can contribute to nerve cell death and accelerate the progression of Parkinson’s disease. This raises the logical question of whether drugs can be developed to selectively target cytokine up-regulation in glia, with the hope that such drugs would attenuate disease progression.
Project Description:
In our Center for Drug Discovery and Chemical Biology, we are using a drug discovery platform that integrates what we call “smart chemistry” with “smart biology” to develop new small molecule compounds that selectively suppress the overproduction of proinflammatory cytokines in the brain. We have developed two exciting new drug-like compounds, named Minozac and Minokine, that are safe in animals, readily enter the brain, and are able to be taken by mouth. We have found that these compounds work by different mechanisms, but both suppress the excessive glial cytokine production back towards normal levels, which prevents subsequent nerve cell damage and behavioral deficits in multiple animal models of neurodegenerative disorders. This project will test these two compounds for effectiveness in an animal model of Parkinson’s disease.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Successful completion of this project will provide substantial impetus for further development of these compounds into future, potentially disease-modifying drugs for Parkinson’s disease.
Anticipated Outcome:
We hope to see that our compounds are effective at suppressing cytokine overproduction in the animal model and preventing the behavioral and nerve cell deficits. We anticipate that positive outcomes would have an immediate impact based on the potential of a clinical development campaign decision by industry for development of a new class of drugs based on our compounds.