New Technology Proves Key to Parkinson's Disease Treatment
Taiwan has approximately 50,000 to 100,000 Parkinson's disease patients, but there is currently no cure. Levodopa is an important medication for treating Parkinson's disease, but its concentration is difficult to control. When the concentration is too high, it can cause side effects such as nausea and vomiting. A research team led by Professor Yi-Chun Yeh from the Department of Chemistry at National Taiwan Normal University has developed a new thermostable enzyme derived from the thermophilic bacterium Streptomyces sclerotialus. Using a red fluorescent signal, this enzyme can detect the presence of levodopa in just 30 minutes, potentially improving the safety of levodopa treatment.
Parkinson's disease, which predominantly affects individuals over 60 years old, is a movement disorder characterized by the rapid degeneration of cells in the basal ganglia and substantia nigra regions of the brain. These cells are responsible for producing an essential neurotransmitter called dopamine. When these cells degenerate, they fail to produce sufficient dopamine, leading to various motor symptoms. To compensate for the deficiency, dopamine precursor "levodopa" is administered because dopamine itself cannot cross the blood-brain barrier. Once converted to dopamine by enzymes in the brain, it effectively alleviates symptoms. It is currently recognized as the most effective treatment for Parkinson's disease.
Professor Yi-Chun Yeh's laboratory specializes in synthetic biochemistry, particularly focusing on neurotransmitters associated with Parkinson's disease. Unlike conventional chemistry, which involves synthesizing small molecules in bulk, synthetic biochemistry utilizes organisms like bacteria, leveraging their self-replicating capabilities to transform them into useful substances. This method eliminates the need to repeat reactions from scratch for each experiment.
Generally, doctors prescribe different dosages of levodopa based on the patient's weight and age, but individual variations in metabolism make it difficult to monitor levodopa concentrations effectively. With the advent of "personalized medicine," Yeh explains that the laboratory aims to develop low-cost, real-time detection tools to enable Parkinson's disease patients to have their medication concentrations monitored immediately. However, it is impractical for patients to cultivate bacteria at home, and the chemical structure of dopamine is very similar to that of levodopa, making it technically challenging to differentiate and detect these structurally similar substances.
However, without "pretreatment" of dopamine and levodopa, concentration detection can easily be distorted. The research team has successfully applied a novel thermostable enzyme from the thermophilic bacterium Streptomyces sclerotialus, specifically 2,3-Dopa-dioxygenase, for the first time in levodopa monitoring. This enzyme serves as an ideal tool for developing protein- and cell-based biosensors.
The laboratory has developed a continuous analysis method using dual-color fluorescent signals, which enables highly sensitive detection of dopamine and levodopa, even when both are present. This approach overcomes the challenge of traditional detection methods in distinguishing structurally similar molecules. By utilizing red fluorescent signals, they have successfully circumvented previous extraction difficulties and can now detect levodopa within just 30 minutes. This real-time monitoring capability holds promise for providing Parkinson's disease patients undergoing levodopa treatment with more immediate, effective, and safe screening options.
Dr. Yeh reflected that the research journey from initial conception to achieving research outcomes took her team at least five years. Each study involved significant time investments, and any error at any stage could lead to experimental failure. Therefore, much time was dedicated to overcoming setbacks, trial and error, and adjusting experimental methods along the way. She noted that this research was a collaborative effort involving multiple cohorts of master's students, and the amount of time and effort expended can hardly be quantified.
Yeh said that this research aims to provide a diagnostic tool for clinical healthcare, enhancing monitoring of Parkinson's disease treatment and potentially significantly improving patients' quality of life. However, the tool has not yet reached the clinical application stage. Currently, testing is being conducted using bovine and equine serum, as well as commercially available artificial urine. Nevertheless, the system's robustness and applicability have been successfully validated in serum samples.
Yeh also said that with over a quarter of Taiwan's counties and cities entering super-aged society, if the laboratory's proposed basic detection tool proves feasible, it could indeed offer Parkinson's disease patients a more cost-effective, user-friendly, and safe method for concentration monitoring. This advancement not only holds promise for improving patient quality of life, but also paves the way for new directions in clinical applications of enzyme-based biosensors. (This article was provided by The Center of Public Affairs.)
Source：Chang, C. W., Lin, Y. H., Tsai, C. H., Kulandaivel, S., & Yeh, Y. C.(2022).Sequential detection of dopamine and L-DOPA by a 2,3-dopa-dioxygenase from Streptomyces sclerotialus.Analytica Chimica Acta, 1202, 339641. https://doi.org/10.1016/j.aca.2022.339641