New Findings on Parkinson’s Treatment Reveal Potential Role for Ketamine
Researchers from the University of Arizona have shed light on a significant challenge faced by individuals with Parkinson’s disease: the development of uncontrollable movements after prolonged medication use. These movements, known as levodopa-induced dyskinesia, arise after years of treating Parkinson’s with levodopa, a medication that the brain converts into dopamine to manage the disorder’s symptoms.
Parkinson’s disease is characterized by a decline in dopamine levels, affecting movement. Although levodopa helps replenish dopamine, long-term use can lead to involuntary movements. A recent study published in the journal Brain explores the underlying mechanisms and potential treatment options for this complication, particularly focusing on the anesthetic ketamine (source).
Lead author Abhilasha Vishwanath, a postdoctoral research associate, explains that the brain adapts to levodopa over time, which contributes to the onset of dyskinesia. Their study found that during these episodes, the motor cortex – the brain area that controls movement – becomes “disconnected,” contradicting previous beliefs that this region actively causes the movements.
“Because of the disconnect between motor cortical activity and these uncontrollable movements, there’s probably not a direct link, but rather an indirect way in which these movements are being generated,” Vishwanath noted.
By recording activity from thousands of neurons in the motor cortex, the team observed minimal correlation between neural firing patterns and dyskinetic movements. This suggests a fundamental disconnection rather than a direct cause-and-effect relationship. As Stephen Cowen, senior author and associate professor, metaphorically described, “It’s like an orchestra where the conductor goes on vacation.”
The study also highlights ketamine’s potential to address dyskinesia. Researchers found that ketamine can interrupt the abnormal neural patterns seen during dyskinesia, possibly allowing the motor cortex to regain control over movement. Cowen stated, “Ketamine works like a one-two punch.” Initially, it disrupts these patterns, and later, it facilitates neuroplasticity, enabling neurons to form and strengthen connections.
Vishwanath mentioned that a single ketamine dose could yield lasting benefits, with effects visible even months later. This finding is especially relevant as a Phase 2 clinical trial is underway at the University of Arizona, testing low-dose ketamine infusions for dyskinesia. Early results look promising, with some patients experiencing prolonged relief.
Adjusting ketamine dosages could enhance therapeutic benefits while minimizing side effects, according to Cowen. The study’s insights into motor cortex involvement may pave the way for novel treatment strategies. Cowen concluded, “By understanding the basic neurobiology underlying how ketamine helps these dyskinetic individuals, we might be able to better treat levodopa-induced dyskinesia in the future.”
The study was funded by the National Institute of Neurological Disorders and Stroke (grants R56 NS109608 and R01 NS122805) and the Arizona Biomedical Research Commission (grant ADHS18-198846).
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