Study Rationale:
About 10 percent of people with Parkinson disease (PD) carry changes in the GBA gene that cause malfunction of a protein called glucocerebrosidase (GCase). People with Parkinson’s whose GCase functions as it should may not have enough of the protein. The malfunction of the GCase protein also contributes to cell damage caused by alpha-synuclein, a sticky protein the clumps in the brains of people with PD. That is why it is so important to create a convenient method of measuring levels of active (properly functioning) GCase in tissues, such as the blood, of people with Parkinson’s disease. Since exiting methods do not unreliably measure GCase levels in the blood, alternatives are needed.
Hypothesis:
We aim to create molecules that can tag GCase by sticking to it in tissues of people with PD to make it simple to track the levels of this protein.
Study Design:
Building on our previous work, we will create a simple method to rapidly measure the level of GCase in tissues of people with PD. We will produce chemicals called probes that specifically tag GCase, making it clearly visible in fluorescent light. We will first confirm that this tagging method works effectively in blood cells of people with Parkinson’s and then compare our measurement of GCase levels with those performed using other techniques.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
Using our new GCase probes, researchers would be able to accurately track both GCase activity and levels in blood samples of people with Parkinson’s disease. This method could prove useful for monitoring disease progression, selecting participants for trials, conducting fundamental clinical research and evaluating disease-modifying agents.
Next Steps for Development:
After the usefulness of our probe is confirmed, it will be shared with other clinical research groups for independent testing and use. If successful, this study would help create new tests for general clinical use.