Small Molecule Drug Therapy for Parkinson's Disease

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DESCRIPTION (provided by applicant): The total cost of caring for Parkinson's disease is about $25 billion per year in the United States. There is an urgent and unmet need for an effective treatment for the patients who have suffered debilitating loss of neurons and motor function. Development of neuroregeneration therapy is an important goal because neurdegenerative diseases disable and kill millions of people worldwide each year, yet a viable therapeutic option is not available. Discovery of neural stem cells in the aging and diseased brain has sparked interest in the development of new approaches to boost the body's natural ability to create healthy new cells from endogenous stem cells. Recently, we made the serendipitous discovery that a small molecule heterocyclic pyrimidine derivative can speed up the growth of human neural stem cells grown in culture. Subsequent preliminary analysis in rodents suggested that the molecule also accelerate neurogenesis in aged brain and improve motor function in dopaminergic lesion mouse, a Parkinson's disease model, apparently without any side effects. Based on these preliminary observations, we are hypothesizing that administration of the heterocyclic pyrimidine derivative will stimulate new brain cell formation leading to improved motor function. To establish proof of concept, we are proposing to conduct a series of studies with a mouse model of Parkinson's disease. We investigate whether the heterocyclic pyrimidine derivative has a potential to protect and/or regenerate neurons by stimulating proliferation, migration and differentiation of endogenous neural stem cells using Immunohistological assays, Western blot, and behavioral tests. Upon the completion of these experiments, we expect to confirm the feasibility of using the heterocyclic pyrimidine derivative to promote dose dependent improvement in motor function associate with neurogenesis in animal model for Parkinson's disease without inducing obviously deleterious effects. In Phase II, we will conduct detailed safety, distribution, and efficacy studies on the molecule with non-human primate Perkinson's disease model, in preparation for carrying out IND enabling studies during Phase III. This project is innovative because our test compound offers a novel approach for inducing new brain cell growth in patients with neurodegenerative diseases. PUBLIC HEALTH RELEVANCE: We are proposing to test a new small molecule drug candidate that can boost the body's natural ability to regenerate brain cells from endogenous stem cells. When successful, our drug candidate will offer a new treatment alternative for patients with neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease and ALS.