Longitudinal changes in the neurovascular response in a rat model of L-DOPA induced Dyskinesia

One of the side effects of taking levodopa to relieve the symptoms of Parkinson’s is that, over time, most people taking the drug develop erratic, involuntary movements called dyskinesia.

Developing dyskinesia often requires people to lower their dosage of levodopa – meaning they don’t get full relief of the stiffness, tremors, and rigidity that characterize Parkinson’s.

At the University of Manitoba, Samuel Booth, a Ph.D. candidate, is looking for ways to predict who will develop dyskinesia and how to prevent this debilitating side-effect.

Booth is using Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) to scan the brains of animal models shortly after they begin getting levodopa.

The neuroscientist is seeking changes in blood flow and metabolism in the brain. He also hopes to discover why most people taking levodopa eventually develop dyskinesia, but some do not.

“There has been some promising data in dyskinesia patients that there’s an abnormality in how the brain is regulating blood flow,” Booth says. “That’s prompted me to look at how blood flow to different brain regions is regulated as well.”

Booth’s work could identify vascular changes in the brain the imaging scans could spot.

If he finds changes, clinicians could use them to predict who is most at risk of developing dyskinesia – or pinpoint a new target for drugs to regulate these systems in the brain, preventing dyskinesia.

“Dyskinesia symptoms can be stigmatizing,” Booth says.

Booth, whose late grandfather had Parkinson’s, watched him have to give up painting when his motor symptoms made it too difficult to continue the pursuit he loved.

“I saw how [Parkinson’s] can affect somebody’s quality of life,” he says.

Relieving this side-effect would improve people’s ability to live with Parkinson’s, he adds.

“If there was some intervention that could prevent dyskinesia development, based on this research, that would be a big improvement in a person’s quality of life,” he says. “It would mean they could continue to take the dose of levodopa that’s effective in relieving Parkinson’s symptoms.”

Booth, who has long been fascinated by the circuitry in the brain, chose a research career because he enjoys designing experiments and solving problems.

He hopes this project will give him the promising data he needs to pursue a further, longer clinical trial involving people with Parkinson’s.