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Evaluation of a LRRK2 Inhibitor in the Partial 6-OHDA-lesioned Model of Parkinson’s Disease

Mutations in the LRRK2 gene are the most common cause of familial Parkinson’s disease (PD). The existing human genetic, cell-based and model data suggest that LRRK2 kinase inhibition might be beneficial in treating Parkinson’s disease.  However, pre-clinical validation of LRRK2 inhibition in treating Parkinson’s disease remains to be demonstrated with a specific LRRK2 kinase inhibitor drug.

Project Description:
The primary goal of this research project is to determine whether LRRK2 kinase inhibition can provide symptomatic or disease-modifying benefits in a non-LRRK2 based pre-clinical PD model. The 6-OHDA partial lesion model offers robust behavioral symptoms and gradual neurodegeneration during a period of several weeks. This study will examine if a LRRK2 compound in this model can reverse the behavioral deficits and/or prevent dopaminergic neurodegeneration.

Relevance to Diagnosis/Treatment of Parkinson’s Disease:
This project will proof-of-concept as to whether LRRK2 kinase inhibition can provide symptomatic or disease-modifying benefits in non-LRRK2 based pre-clinical PD model. If positive, these types of drugs may be used to treat idiopathic Parkinson’s patients.

Anticipated Outcome:
The anticipated outcome is that this LRRK2 kinase inhibitor will be efficacious in this model. This may provide supporting evidence that this class of drug will ameliorate the symptoms and/or have disease-modifying potential in Parkinson’s patients.


  • Kimberly Scearce-Levie, PhD

    South San Francisco, CA United States

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