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Funded Studies

Use of LRRK2 and Lysosomal Biomarker Signatures to Differentiate Idiopathic and Monogenetic Parkinson’s Disease

Study Rationale:    
As new targeted therapies for Parkinson’s disease (PD) enter clinical trials, it will be important to develop biomarkers that will allow clinicians to match people with PD with the most appropriate clinical trial or treatment. Here, we will use state of the art technologies to analyze peripheral blood and urine samples from two populations: people with a genetic form of PD and those whose PD is idiopathic (cause unknown). In particular, we will assess the activation status of LRRK2, a major hereditary factor in PD, and the dysfunction of the lysosome, an important cell organelle for clearing cell debris. 

We hypothesize that assessing biomarkers for LRRK2 activation and lysosomal dysfunction in blood and urine will allow us to define the subtype-specific disease signatures of idiopathic and genetic PD and will identify the most appropriate tests for future studies.  

Study Design:
We will use an existing collection of several hundred peripheral blood and urine samples from people carrying genetic changes in PD-associated genes including LRRK2, VPS35 and GBA, as well as idiopathic PD and controls. These samples were collected and prepared according to protocols that we developed. We will deploy established and novel state-of-the-art techniques for analyzing LRRK2 pathway activity and lysosomal dysfunction and additional tests in this unique sample set. 

Impact on Diagnosis/Treatment of Parkinson’s Disease:
The proposed research has the potential to identify subtype-specific disease signatures that may help with predicting treatment response or clinical course. In addition, the results should allow us to identify the most suitable tests for future studies of the LRRK2 signaling pathway. 
Next Steps for Development:
If successful, our study may help with better patient stratification and bring us a step closer to better understanding Parkinson's disease.


  • Esther Sammler, MD, PhD

    Dundee United Kingdom

  • Dario Alessi, PhD

    Dundee United Kingdom

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