Researchers at the University of Arizona have shed light on a common and troubling side effect of long-term Parkinson’s disease treatment: uncontrollable movements known as levodopa-induced dyskinesia.
Their findings, published in the journal Brain, not only explain how these movements arise but also explore the potential of ketamine, an anesthetic, to manage the condition.
Parkinson’s disease is a neurological disorder caused by the gradual loss of dopamine, a brain chemical essential for coordinating movement.
To compensate, patients are often prescribed levodopa, a drug that converts into dopamine in the brain.
While levodopa is highly effective in the early stages of treatment, years of use often lead to dyskinesia, marked by involuntary, erratic movements. This side effect significantly impacts patients’ quality of life.
The research team discovered that dyskinesia stems from changes in how the brain adapts to levodopa over time.
Specifically, they found that the motor cortex—the part of the brain responsible for movement—becomes “disconnected” during dyskinetic episodes. This challenges the previous belief that the motor cortex directly causes these movements.
Dr. Abhilasha Vishwanath, the study’s lead author, explained, “The disconnect between motor cortical activity and these uncontrollable movements suggests an indirect mechanism rather than a direct one.”
The researchers recorded signals from thousands of neurons in the motor cortex and found that the patterns of activity had little connection to the dyskinetic movements.
“It’s like an orchestra playing without a conductor,” added Dr. Stephen Cowen, senior author of the study. “Without the motor cortex coordinating movement, other neural circuits seem to take over, leading to these problematic movements.”
The study also highlighted ketamine’s potential as a treatment for dyskinesia. Ketamine appears to disrupt the abnormal brain activity associated with these movements.
It works in two stages: first, it interrupts the repetitive electrical patterns in the brain that occur during dyskinetic episodes. Then, over time, it promotes neuroplasticity—the brain’s ability to form and strengthen connections between neurons.
“Ketamine works like a one-two punch,” said Cowen. “Its immediate effects calm the abnormal activity, while its longer-lasting effects help the brain reorganize and regain some control over movement.”
Remarkably, a single dose of ketamine has shown benefits that last for weeks or even months in some cases, according to Vishwanath.
These findings are being tested further in a Phase 2 clinical trial at the University of Arizona. Early results suggest that low-dose ketamine infusions can provide long-lasting relief from dyskinesia, with minimal side effects.
Researchers are optimistic about fine-tuning doses or developing new therapies inspired by ketamine’s effects.
The study’s implications go beyond managing dyskinesia. By understanding how the motor cortex contributes to Parkinson’s symptoms, scientists hope to develop more effective treatments that target the root causes of movement disorders.
“By uncovering the basic neurobiology of ketamine’s benefits, we can pave the way for better therapies to treat levodopa-induced dyskinesia in the future,” Cowen said. These advancements offer hope for improving the lives of Parkinson’s patients grappling with this challenging condition.
If you care about Parkinson’s disease, please read studies about Vitamin E that may help prevent Parkinson’s disease, and Vitamin D could benefit people with Parkinson’s disease.
For more information about brain health, please see recent studies about new way to treat Parkinson’s disease, and results showing COVID-19 may be linked to Parkinson’s disease.
The research findings can be found in Brain.
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