Funded Studies
Objective/Rationale:
LRRK2 variants significantly contribute to the development of familial and sporadic Parkinson’s disease (PD). However, it is not yet understood how LRRK2 mutations cause cellular dysfunction, why they do not always lead to disease, and why age at onset of disease can vary from 30 to 90 years. The aim of the study is to set up a robust, widely usable assay (characterization test) to monitor LRRK2 function and associated disease in a clinical setting.
Project Description:
Within this project researchers will use a colony-forming cell (CFC) assay to assess and compare blood cell development (hematopoiesis) on a cellular level in LRRK2 PD patients, asymptomatic LRRK2 mutation carriers and control individuals. The ultimate goal of this project is to improve an already established monocyte differentiation assay with respect to clinical applicability in laboratories worldwide. Additionally, they will test the effect of different LRRK2 inhibitors on hematopoiesis looking for potentially relevant effects for PD treatment.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
By applying the CFC assay, researchers aim to find significant differences in hematopoietic cells between LRRK2 mutation carriers (with and without PD) and healthy controls. They speculate that these alterations in hematopoiesis are detectable decades before the appearance of symptoms. Therefore, they believe that the CFC assay is a suitable tool for early diagnosis of LRRK2-associated PD.
Anticipated Outcome:
Investigators expect to learn more about cellular modifications in blood as response to progressive cell degeneration in the brains of PD patients. They believe that the CFC assay can detect molecular crosstalk between pathologic brain and blood and related cellular modifications in the blood. Furthermore, they expect to learn more about the impact of LRRK2 on hematopoiesis and a possible role in the progression of Parkinson´s disease.