Ketamine may help address levodopa-induced dyskinesia in Parkinson’s disease, according to a new study.
Levodopa is administered to Parkinson’s patients to help counter the loss of dopamine that contributes to the condition. However, after years of this treatment, many patients experience involuntary and uncontrollable movements known as levodopa-induced dyskinesia.
In a new study, researchers have now discovered that the brain’s motor cortex, responsible for controlling movement, becomes disconnected during dyskinetic episodes.
They found that the firing patterns of brain neurons showed little correlation with the dyskinetic movements, suggesting a fundamental disconnection rather than direct causation, challenging the currently prevailing view that the motor cortex actively generates these uncontrollable movements.
According to lead researcher Abhilasha Vishwanath at the University of Arizona, 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.
“There are about 80 billion neurons in the brain, and they hardly shut up at any point. So, there are a lot of interactions between these cells that are ongoing all the time,” Vishwanath said.
“It’s like an orchestra where the conductor goes on vacation,” said Stephen Cowen, senior author of the study.
“Without the motor cortex properly coordinating movement, downstream neural circuits are left to spontaneously generate these problematic movements on their own.”
Ketamine as a treatment
Previous work from the team has shown the potential of the common anaesthetic ketamine as a therapy for the problem.
In the work, the team showed that ketamine could help disrupt abnormal repetitive electrical patterns in the brain that occur during dyskinesia – potentially helping the motor cortex to regain some control over movement.
This works as ketamine initially disrupts abnormal electrical patterns occurring during dyskinesia, then later triggers much slower processes that allow for changes in the connectivity and activity of brain cells over time, known as ‘neuroplasticity’.
The team said their work shows that beneficial effects can be seen even after a few months with just one dose of ketamine.
A Phase 2 clinical trial is now being conducted, testing low doses of ketamine infusions as a treatment for the condition which the researchers say has shown promising early results.
According to Cowen, ketamine doses could be tweaked in a way such that the therapeutic benefits are maintained with minimised side effects, and entirely new therapeutic approaches could be developed based on the study’s findings about motor cortex involvement in dyskinesia.
“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,” Cowen said.
