Investigator:
Giulietta Riboldi, MD
Name of Institution:
NYU Langone Health, New York, New York
Project Title:
Role of GBA mutation in the pathogenesis of Parkinson’s disease (PD)
Investigator Bio:
Dr. Riboldi is a post-doctoral fellow at the Fresco Institute for Parkinson’s disease and Movement Disorders at NYU Langone Health. She received her MD at the University of Milan (Italy) where she also completed her Neurology Residency. Before joining NYU, she worked as a post-doctoral fellow at Columbia University’s Motor Neuron Center where she studied the molecular mechanisms of neurodegenerative disorders.
Objective:
The goal of this project is to better understand the role of glucocerebrosidase (GBA) mutations in the pathogenesis of PD.
Background:
GBA is an enzyme that breaks down a large molecule called glucocerebroside, thereby keeping it from accumulating in cells. Mutations in both copies of the GBA gene, in which glucocerebroside does accumulate, is the cause of Gaucher’s disease. Mutations in one (or both) copies of the GBA gene is also a genetic risk factor for development of PD. However, only a small percentage of GBA carriers develop the disease and it is not yet clear why some people with the mutation develop it and others do not. This project investigates whether interaction with other genetic modifiers is responsible for the pathogenicity of GBA mutations in susceptible subjects.
Methods/Design:
We will analyze the genomic profile of monocytes, a cell type of the immune system which may play a role in the pathogenesis of PD. We will compare the results from a group of GBA carriers affected with PD, with a group of GBA carriers unaffected with PD. We hope to uncover genetic differences that can change GBA function and contribute to disease. In addition, the clinical profiles of the GBA carriers who developed PD and the GBA carriers who did not develop PD will be compared to look for consistent differences between the two groups.
Relevance to Diagnosis/Treatment of Parkinson’s disease:
Growing evidence supports the central role of GBA mutations in the development of PD. The identification of mechanisms that could explain the pathogenicity of the GBA mutation may allow for the identification of new therapeutic targets. In addition, understanding this process can help identify biomarkers among carriers of the GBA mutation who are at an increased risk of developing the disease.