A protein in the brain known as glucocerebrosidase may not work properly in those with Parkinson's disease (PD). Methods currently used to monitor the activity of this protein within living cells are limited, making it difficult to study changes in glucocerebrosidase activity within an individual or to compare levels of its activity across individuals. For these reasons, there is a need for a sensitive, convenient and accurate way to measure glucocerebrosidase in blood cells.
We hypothesize measuring glucocerebrosidase activity in live cells could help provide an earlier diagnosis of PD and predict disease progression, as well as evaluate the efficacy of glucocerebrosidase-targeted therapies.
We will create probe molecules to monitor glucocerebrosidase activity in live blood cells by synthesizing new probes with improved properties We will then test these probes and identify the best probe molecule to advance into further testing. Finally, we will develop a suitable assay (test) to monitor glucocerebrosidase activity in live cells and will evaluate the activity of this protein in cells from those with PD.
Impact on Diagnosis/Treatment of Parkinson's disease:
We expect that clinicians will be able to accurately monitor glucocerebrosidase activity in blood samples from those with PD using our assay. This method could help provide an earlier diagnosis of PD and predict disease progression, as well as evaluate the efficacy of glucocerebrosidase-targeted therapies. As blood sampling is a very simple technique, this assay could prove widely useful.
Next Steps for Development:
This project will establish a proof-of-principle study for this assay and its use in the clinic to measure glucocerebrosidase activity in live blood cells from those with PD. Next steps for this project include establishing a standardized clinical assay and demonstrating its use across large-scale efforts in various clinics.