Study Rationale:
Changes in the GBA1 gene are the most common known genetic risk factor for Parkinson’s disease (PD). This gene encodes the enzyme glucocerebrosidase (GCase), which helps break down certain lipids, including the toxic lipid glucosylsphingosine. Many clinical trials target GCase to modify PD. To develop better treatments, researchers urgently need simple blood tests (“biomarkers”) that can show whether a drug is hitting its target, and whether it might be helping. In this project, we will test if dried blood spots can be used for GBA1-related biomarkers.
Hypothesis:
We aim to test if measurements of GBA1-related biomarkers from dried blood spots are reliable and informative across different laboratories. This will help the design of biomarker collection in GBA1-related Parkinson’s disease clinical trials.
Study Design:
Centogene will identify 120 dried blood spot samples (60 from GBA1 carriers and 60 from non-carriers) and ship the samples to Tel Aviv Medical Center for blinding. Tel Aviv Medical center will distribute the samples to three expert laboratories, Ravvity, Nextcea and Centogene. Each lab will measure GCase activity and related lipids in the dried blood spots. We will then compare the results to see how similar they are across laboratories and how well these measurements reflect the person’s GBA1 genetic status.
Impact on Diagnosis/Treatment of Parkinson’s disease:
By the end of the study, we expect to know which measurements from dried blood spots are most reliable and informative, and how consistent they are across different laboratories. This will help the design of biomarker collection in GBA1-related Parkinson’s disease clinical trials.
Next Steps for Development:
We estimate that the data generated here will be used by teams, which design and execute clinical trials targeting the GBA1 pathway.