Optimization of Nigrostriatal Degeneration in the Alpha-synuclein Preformed Fibril Model
Research Grant, 2016
Pre-clinical models of Parkinson's disease (PD) can provide clues to disease mechanisms and serve as a platform to test novel treatment strategies. We have previously established that intra-striatal (brain region associated with PD) injection of preformed alpha-synuclein fibrils can result in pathology and loss of nigrostriatal dopamine. This proposal outlines steps to optimize this alpha-synuclein preformed fibril PD model.
We hypothesize that by using optimized surgical parameters we can establish a pre-clinical preformed alpha-synuclein PD model that will result in damage to approximately 75% of nigrostriatal dopamine neurons and consistently measurable behavioral impairments.
We will test the effects of varying the amount and distribution of preformed alpha-synuclein on the survival of nigrostriatal dopamine neurons and motor performance.
Impact on Diagnosis/Treatment of Parkinson's Disease:
The alpha-synuclein preformed fibril model could facilitate pre-clinical assessment of novel disease-modifying therapies.
Next Steps for Development:
Following successful optimization, external validation studies could be conducted in the alpha-synuclein preformed fibril model to make direct comparisons to clinical metrics used in the assessment of PD (e.g., levodopa responsiveness, longitudinal imaging studies).
Professor and Associate Chair at Michigan State University
Location: Grand Rapids, Michigan, United States