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Funded Studies

Investigating the Neuroprotective Potential and Mechanism of Action of an Inhibitor of the Rho-associated Protein Kinase (ROCK)

Study Rationale: Altered signaling through the Rho-associated protein kinase (ROCK) pathway has been found to play a role in the cellular pathogenesis of Parkinson’s disease (PD). Previously, we demonstrated that inhibition of ROCK with the compound KL-00974 can protect dopamine-producing neurons from toxic effects of alpha-synuclein aggregation. In this study, we will determine the optimal dosage and administration protocol for using KL-00974 to target ROCK in the brain.

Hypothesis: Daily administration of optimized dosing of KL-00974 will mitigate the overproduction of alpha-synuclein and the toxicity and degeneration induced by preformed alpha-synuclein aggregates.

Study Design: We will leverage the particular strengths of two different preclinical alpha-synuclein PD models to determine the mechanism and potential of KL-00974 to provide neuroprotection for dopamine-producing neurons in the brain.

Impact on Diagnosis/Treatment of Parkinson’s disease: Positive results in this proposal could lead to the identification of a novel pharmacologic compound for disease modification in PD.

Next Steps for Development: Success in this proposal will lead to an application to the FDA to move forward to human testing of KL-00974 for the treatment of PD.


Researchers

  • Caryl E. Sortwell, PhD

    Grand Rapids, MI United States


  • Jeffrey P. MacKeigen, PhD

    Grand Rapids, MI United States


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