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.
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.
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.