Peripheral Blood-based Transcript Biomarkers for Prediction of Parkinson Disease in LRRK2 Mutation Carriers
LRRK2 Cohort Consortium Resource Request, 2013
Objective/Rationale: † † † † † ††
Currently, there is no known marker that can be found in the human blood that can help to predict Parkinson's disease (PD). There is also no marker that can help identify among asymptomatic people who carry a LRRK2 gene mutation (the greatest known genetic contributor to PD) who will convert to PD. We aim to detect such a marker in the blood, based on a specific gene expression pattern.
An unbiased scan of all sets of RNA molecules in the blood (transcriptome) will be performed using the methodology of massive parallel sequencing (RNASeq). We aim to determine the best RNASeq conditions that will allow meaningful transcriptomic analysis and the identification of low magnitude expression changes. Our analysis will proceed through two stages. First, we will evaluate various sequencing depths using RNA derived from whole cellular blood as well as from white blood cells. Secondly, we will perform a proof-of-concept study to estimate the feasibility of RNA sequencing-based markers in asymptomatic LRRK2 carriers.
Relevance to Diagnosis/Treatment of Parkinsonís Disease: † † † † † † † † † † †
If this feasibility study is successful, a blood marker might be developed that predicts conversion to PD in asymptomatic carriers of the LRRK2 mutation. Such a marker may facilitate therapeutic interventions at a pre-symptomatic disease stage.
Anticipated Outcome: † † † † †
Here we propose to develop evidence to prove the concept of a non-invasive, accurate and affordable blood test with the potential to predict the conversion of carriers of LRRK2 mutations from pre-symptomatic stage to full disease. This molecular blood biomarker might also provide insight into disease mechanisms and novel targets for PD therapy.
Head of the Neurogenomics Lab and the Parkinson Personalized Medicine Initiative at Harvard and Brigham and Womenís Hospital
Associate Professor of Neurology at Harvard Medical School
Location: Cambridge, Massachusetts, United States
Director, Genetic Institute at Tel Aviv Sourasky Medical Center
Location: Tel Aviv, Israel