Study Rationale:
New pre-clinical models have been developed to study the hypothesis that damaging forms of alpha-synuclein (protein involved in Parkinson's) spread across brain regions from a single point of origin. The current study's objective is to validate this novel model to develop standard operating procedures so that industry and academic groups can reproduce it.
Hypothesis:
Preformed fibril alpha-synuclein injected into a single brain region will reproducibly spread to adjacent brain areas and produce pathology that can be used as end points in pre-clinical efficacy testing.
Study Design:
Alpha-synuclein preformed fibrils will be injected into a single specific motor area. Over the course of six months, pre-clinical models will be evaluated on motor performance. At three time points, we will examine the brains for spread of alpha-synuclein and related pathology.
Impact on Diagnosis/Treatment of Parkinson's Disease:
Production and validation of a model of alpha-synuclein spread will prove valuable to understanding inherent mechanisms and thereby development of treatments aimed at preventing spread. Furthermore, production of such a platform will allow for evaluation of treatment effects on multiple brain regions simultaneously to address non-motor regions involved in Parkinson's.
Next Steps for Development:
Successful validation and implementation of this model will encourage wide spread use and thereby provide a platform for multiple investigators to use the same platform from which to benchmark novel treatment strategies to bring forth into the clinic.