Assessing Glucocerebrosidase in Sporadic Parkinsonís Disease
Biosample and Tissue Resource, 2013
Objective/Rationale: † † † † † ††
Mutations in the glucocerebrosidase (GBA) gene are the most common genetic risk factor for Parkinsonís disease (PD). These mutations are present in approximately seven percent of PD patients. The aim of this project is to determine whether the GBA protein (coded by the GBA gene) is altered in the majority brains of sporadic (cause unknown) PD patients without these mutations. These data will guide the therapeutic development of GBA-targeted therapies for PD.
Project Description: † † † † † ††
Brains from sporadic PD patients without GBA gene mutations will be compared to two groups: aged controls and PD patients with GBA mutations. Two key aspects ó GBA protein levels and its enzymatic activity ó will be analyzed. If the GBA protein is altered, further experiments will be undertaken to understand the mechanism of these changes. In addition, the relationship between levels in cerebrospinal fluid and in the brain will be tested.
Relevance to Diagnosis/Treatment of Parkinsonís Disease: † † † † † † † † † ††
Understanding the changes in the GBA protein and their mechanisms will allow for development of targeted therapies for PD patients. Experiments in cerebrospinal fluid may enable targeting therapies towards subpopulations of PD patients with changes in GBA who would be most likely to benefit.
Anticipated Outcome: † † † † †
Demonstrating changes in GBA will provide a strong rationale for development of GBA-targeted therapies for sporadic PD patients. Understanding of the underlying mechanism responsible for these changes will allow generation of more predictive cell and pre-clinical models, as well as development of therapies targeted at this specific mechanism.†
Consultant at The Boston Consulting Group
Location: Boston, Massachusetts, United States
Director of Neurology Research at Biogen
Location: Cambridge, Massachusetts, United States