0
0
University of Arizona researchers uncover new insights into levodopa-induced dyskinesia and potential treatments
A groundbreaking study from the University of Arizona (U of A) has reshaped scientific understanding of one of Parkinson’s disease’s most debilitating complications: levodopa-induced dyskinesia (LID). Published in the journal Brain, the research explores how this condition arises and reveals how the anesthetic ketamine may offer a promising therapeutic avenue.
Parkinson’s disease is a progressive neurological disorder characterized by diminished dopamine levels, a chemical essential for motor function. Levodopa, the standard treatment, helps restore dopamine levels, but long-term use often results in dyskinesia—uncontrollable and involuntary movements that significantly impact patients’ quality of life.
The study’s lead author, Dr. Abhilasha Vishwanath, a postdoctoral researcher at U of A’s Department of Psychology, described a pivotal discovery: during dyskinetic episodes, the motor cortex—responsible for coordinating movement—becomes “disconnected.” This challenges the long-held belief that the motor cortex directly causes these erratic movements.
Rewriting the Neurological Script
“Traditionally, it was thought that the motor cortex actively generates these movements,” Vishwanath said. “But our findings suggest an indirect mechanism is at play.”
The team recorded the activity of thousands of neurons in the motor cortex and observed a lack of correlation between their firing patterns and the dyskinetic movements. Instead, the researchers likened the phenomenon to an orchestra losing its conductor. Without proper coordination from the motor cortex, other neural circuits seem to act independently, leading to involuntary movements.
Dr. Stephen Cowen, senior author of the study and associate professor in the Department of Psychology, explained: “It’s as if the motor cortex has gone offline, leaving downstream circuits to create their own chaotic movements.”
Ketamine’s Role: A New Therapeutic Pathway
In addition to identifying the mechanism behind dyskinesia, the study highlighted ketamine’s potential to alleviate the condition. The anesthetic disrupts abnormal repetitive electrical patterns in the brain associated with dyskinesia, allowing the motor cortex to regain some control.
“Ketamine works like a one-two punch,” Cowen said. “It not only interrupts the problematic patterns during dyskinesia but also promotes long-term neuroplasticity—allowing neurons to form new connections and strengthen existing ones.”
With just one dose of ketamine, some Parkinson’s patients have experienced lasting benefits for months, according to the researchers.
Clinical Trials Show Early Promise
These findings have sparked excitement in the medical community. A Phase 2 clinical trial at U of A is testing low-dose ketamine infusions for dyskinesia in Parkinson’s patients. Early results are encouraging, with participants reporting weeks-long relief after a single treatment.
Dr. Vishwanath emphasized the potential for refining ketamine therapy to maximize benefits while minimizing side effects. “By understanding how ketamine interacts with brain circuits, we could develop entirely new treatments for LID,” she said.
A Brighter Future for Parkinson’s Patients
This study not only deepens the understanding of Parkinson’s-related movement disorders but also opens new avenues for managing levodopa-induced dyskinesia. As researchers refine ketamine-based treatments, they move closer to offering patients longer-lasting relief from one of the most challenging aspects of Parkinson’s disease.
“By uncovering the mechanisms behind dyskinesia and leveraging ketamine’s therapeutic potential, we’re paving the way for more effective and targeted treatments,” Cowen concluded.
For more information, see:
Abhilasha Vishwanath et al, Decoupling of motor cortex to movement in Parkinson’s dyskinesia rescued by sub-anaesthetic ketamine, Brain (2024). DOI: 10.1093/brain/awae386
