A recently developed small-molecule fluorescence probe may play a key role in the future of Parkinson’s disease research and diagnosis.
The probe, developed by researchers from the National University of Singapore (NUS), detects the activity of monoamine oxidase B (MAO-B) — an enzyme that breaks down dopamine and other chemicals in the brain and is found at higher levels in people with Parkinson’s.
In February, researchers from NUS published their findings in the journal Nature Communications. The two-photon, small-molecule fluorogenic probe may allow physicians to more accurately predict patients’ likelihood of developing Parkinson’s disease before they exhibit symptoms, explains Li Lin, PhD, postdoctoral fellow at the Department of Chemistry, Faculty of Science, NUS, and first author of the article.
“Current diagnosis of Parkinson’s disease mainly relies on the patient’s symptoms prior to brain examination,” Li says. “However, by the time the patient’s symptoms become obvious, the disease has already caused severe and irreversible damage to his or her brain cells. So, we have been trying to develop a rapid-detection method to evaluate potential risk for Parkinson’s disease, and the molecular fluorescence probe is a very good choice for its photophysical properties and clinical application.”
At present, the only reliable tests for Parkinson’s disease at the preclinical or diseased stages are costly PET scans that require specialized skills, Li notes.
Although fluorescence-based MAO-B probes exist, some require activating reagents that affect the enzymes’ properties, decreasing accuracy. Other biomarkers can’t distinguish between MAO-B and monoamine oxidase-A, but because the new probe is a substrate of the enzyme, it detects MAO-B without affecting the enzyme’s properties — addressing a significant shortcoming of other biomarkers.
The NUS team found that MAO-B activities also occur in B-lymphocytes — a type of white blood cell — making for a more accessible biomarker that helps clinicians detect the disease promptly.
“Our finding is important, as it suggests that the activity of MAO-B in peripheral blood cells may potentially be used as a convenient surrogate biochemical marker for Parkinson’s disease diagnosis, and perhaps even as a preclinical marker for at-risk individuals who are otherwise asymptomatic,” Li says.
Research has demonstrated that small doses of certain MAO-B inhibitors can slow Parkinson’s disease progression, though the National Parkinson Foundation cautions that additional studies are needed to confirm the findings. Because the new probe has shown no evidence of toxicity, it can potentially be used to monitor MAO-B activities during different stages of disease progression, giving researchers a clearer picture of the disease process.
Additionally, the probe can be used to gauge pharmaceutical efficacy, or the likelihood of patients responding to certain treatments.
“This probe may potentially be useful to monitor patients’ response to medication, which will help physicians to evaluate potential risk for Parkinson’s disease,” Li explains. “In the future, there may be a smart device for clinical use based on this finding.”