Objective/Rationale:
While most PD is not associated with a specific genetic cause, the genetic mutation affecting the LRRK2 gene has been identified as a cause of PD in selected families and populations. We plan to conduct brain imaging in unaffected family members of PD patients with the LRRK2 gene to investigate whether it is possible to detect changes in the brain even before any PD symptoms occur. Early detection of brain imaging changes will help to understand how LRRK2 results in PD, and ultimately, how to best develop medication to prevent the onset of symptoms.
Project Description:
This study is part of a worldwide consortium of PD investigators to evaluate individuals with a LRRK2 gene mutationwho are not yet manifesting any symptoms of Parkinson Disease. We will conduct the brain imaging component of the study. Individuals with a LRRK2 mutation will undergo single photon emission computerized tomography (SPECT) imaging using a radioactive isotope to tag the dopamine transporter, a protein on nerve cells that is reduced in PD. This method is a standard technique that is commonly used to diagnose PD. Using this technique it is possible to determine whether there has been a reduction in dopamine imaging activity even before any PD symptoms might arise. We plan to study whether peoplewith a LRRK2 gene mutation are more likely to show a reduction in DAT imaging compared to those without the gene mutation.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Utilizing DAT SPECT imaging to detect changes in individuals carrying the gene for LRRK2 enables us to study the stage of PD before symptoms occur called the pre-diagnostic period. Identifying and ultimately monitoring the reduction in dopamine imaging in these ‘at risk’ for PD will provide a unique opportunity to study how PD begins in LRRK2 patients and to eventually develop a strategy to develop medications to prevent the onset of PD in LRRK2 gene carriers and potentially for other causes of PD.
Anticipated Outcome:
In collaboration with the LRRK2 consortium, we will use DAT imaging to assess the pre-diagnostic period for individuals with a LRRK2 mutation. The imaging results will be correlated with comprehensive clinical testing to better understand the earliest phase of PD and ultimately to develop medications that might prevent the onset of PD symptoms. The lessons learned from these LRRK2 individuals also will likely provide crucial clues to the causes and treatment of both genetic and non-genetic PD.
Researchers
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Kenneth Marek, MD