Simon Fraser University researchers have uncovered why levodopa, the primary medication for Parkinson's disease, doesn't work equally well for all patients. Using advanced magnetoencephalography (MEG) brain imaging, the team discovered that the drug sometimes activates unintended brain regions, reducing its therapeutic effectiveness.
The study, published in Movement Disorders, represents a collaboration between SFU and Sweden's Karolinska Institute. Researchers examined brain activity in 17 patients before and after taking levodopa, the main drug used in dopamine replacement therapy for Parkinson's disease.
MEG Technology Reveals Off-Target Drug Effects
MEG is an advanced non-invasive technology that measures the magnetic fields produced by the brain's electrical signals. Using this rare brain imaging technology, the research team developed a new analysis method that allows them to "search" the brain for off-target drug effects.
"With this new way of analysing brain imaging data, we can track in real time whether or not the drug is affecting the right brain regions and helping patients to manage their symptoms," says Alex Wiesman, assistant professor in biomedical physiology and kinesiology at SFU.
The researchers mapped participants' brain signals before and after taking the drug to determine how and where levodopa impacted brain activity. Their analysis revealed that in some patients, the drug activates brain regions that shouldn't be activated, interfering with its helpful effects.
Clinical Implications for Personalized Treatment
"What we found was that there are sometimes 'off-target' effects of the drug. In other words, we could see the drug activating brain regions we don't want to be activating, and that's getting in the way of the helpful effects," Wiesman explained. "We found that those people who showed 'off target' effects are still being helped by the drug, but not to the same extent as others."
While levodopa is effective in improving symptoms for the vast majority of patients, not everyone experiences the same level of benefit. The study's findings suggest that understanding how each brain responds to levodopa could help clinicians fine-tune treatment plans, whether through adjusting dosages or trying different medications altogether.
Growing Disease Burden Drives Research Urgency
"Parkinson's is the second most prevalent neurodegenerative disease worldwide and it is the most rapidly increasing, in terms of incidence," notes Wiesman. "Treating this disease, both in terms of helping people with their symptoms, but also trying to find ways to reverse the effects, is becoming more and more important."
Parkinson's disease affects predominantly the dopamine-producing neurons in a specific area of the brain called the substantia nigra. People with the condition may experience movement-related symptoms such as tremors, slow movement, stiffness, and balance problems.
Advanced Imaging Capabilities Enable Breakthrough
SFU's ImageTech Lab, located at Surrey Memorial Hospital, houses the only MEG scanner in Western Canada. The lab's advanced capabilities allowed the research team to gain unprecedented insights into real-time brain-drug interactions.
"If clinicians can see how levodopa activates certain parts of the brain in a patient, it can help to inform a more personalised approach to treatment," Wiesman added.
Broader Applications Beyond Parkinson's
The new brain imaging analysis method isn't limited to studying Parkinson's disease. Any medications that affect brain signaling can be studied using the approach developed by Wiesman and colleagues. The research team hopes their work will lead to faster, more precise, and more widely available personalized treatments for neurological conditions.
"The next phase is to validate our approach in a larger patient cohort and work toward adapting it to more accessible tools like EEG," Wiesman said, indicating the potential for broader clinical implementation of their findings.
