Objective/Rationale:
It is known that a mutation of specific gene, called LRRK2, increases the risks of developing Parkinson’s disease in humans. The specific objective of this proposal is to determine whether a mutation of that same LRRK2 gene in pre-clinical models will lead to an increase in these models becoming more sensitive to a toxin that is used to create other pre-clinical models of Parkinson’s disease.
Project Description:
Using pre-clinical models that carry the LRRK2 mutation and that do not, increasing doses of MPTP will be injected for a period of four weeks. This leads to deficits in movement and nerve cell loss that mimics what is observed in patients with Parkinson’s disease. At the end of four weeks, the preclinical models will be tested on three different motor tasks. It will then be determine if the presence of the toxin resulted in a greater loss of nerve cells and greater deficits in movement in models carrying the LRRK2 mutation compared to those without the mutation.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
The issue of increased sensitivity of pre-clinical models with the LRRK2 mutation to the toxin, MPTP, has direct implications for humans with Parkinson’s disease. If successful, we can then start studying more directly how this mutation affects these models and what therapies can then be used to reverse this affect.
Anticipated Outcomes:
The most important finding from this study will be whether this specific mutation of the LRRK2 gene makes these models more sensitive to developing Parkinson’s disease when injected with the toxin, MPTP. If this is the case, then finding out how this mutation actually works in affecting motor movement and nerve cell loss can lead to more focused treatment of patients with Parkinson’s disease if they carry this same mutation.