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A Novel Preclinical Candidate for Reducing Alpha-synuclein Aggregation in Parkinson’s Disease

Study Rationale: The goal of this program is to develop a novel drug for Parkinson’s disease (PD) with a unique mechanism of action. We have a drug candidate that shows potential as an inhibitor of the aggregation of alpha-synuclein. This drug candidate blocks a molecule called heparan sulfate glycosaminoglycan, which has been associated with alpha-synuclein aggregates and is thought to contribute to their toxic buildup and spread. During this program we will confirm our observations in a larger study and characterize the drug candidate for further clinical development.

Hypothesis: We hypothesize that by blocking heparan sulfate glycosaminoglycan, our drug candidate will inhibit the aggregation and spreading of alpha-synuclein, thereby minimizing neurodegeneration in preclinical PD models.

Study Design: We will first confirm the therapeutic effect of our leading drug candidate in a preclinical animal model of PD. Next, we will synthesize the drug candidate in larger quantities and subject it to a series of preclinical tests to evaluate its drug-like properties, metabolic stability and toxic liabilities. We also plan to optimize the drug for oral delivery.

Impact on Diagnosis/Treatment of Parkinson’s disease: Following the successful completion of these studies, we will have identified a safe and well-tolerated drug candidate. This candidate will be well-positioned for advancement toward Phase 1 studies. If successful, this project could yield a unique, disease-modifying approach to treat PD.

Next Steps for Development: We intend to continue IND-enabling preclinical studies, including optimization of dosing and route of administration and development of a clinical plan. Completion of the activities in this project should position this drug candidate on the pathway to be successful in IND filing and moving into Phase I clinical trials.


Researchers

  • Paul Gregor, PhD

    Lexington, KY United States


  • Patrik Brundin, MD, PhD

    Grand Rapids, MI United States


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