Researchers from the University of Arizona have uncovered new insights into one of the most common complications faced by patients with Parkinson's disease: uncontrolled movements that occur after years of treatment.
Parkinson's disease, a neurological disorder of the brain that affects a person's movements, develops when the level of dopamine, a chemical in the brain responsible for body movements, begins to decrease.
To prevent the loss of dopamine, a drug called levodopa is administered, which is later converted to dopamine in the brain. However, long-term treatment with levodopa causes involuntary and uncontrollable movements known as levodopa-induced dyskinesia.
A study published in the journal Brain has revealed new discoveries about the nature of levodopa-induced dyskinesia and how ketamine, an anesthetic, can help address this challenging condition.
Over the years, the brain of a Parkinson's patient adapts to levodopa treatment, so levodopa causes dyskinesia in the long term. In the new study, the research team found that the motor cortex - the area of the brain responsible for controlling movements - becomes effectively "shut down" during dyskinetic episodes.
Studies have shown that ketamine can help disrupt abnormal repetitive electrical patterns in the brain that occur during dyskinesia. This can potentially help the motor cortex regain control of movement.
Ketamine works in two stages in these patients. First, it disrupts these abnormal electrical patterns that occur during dyskinesia. Then, a few hours or days later, ketamine triggers much slower processes that allow for changes in brain cell connectivity and activity over time, known as neuroplasticity. It lasts much longer than the immediate effects of ketamine. Neuroplasticity is what allows neurons to form new connections and strengthen existing ones.
With a single dose of ketamine, positive effects can be seen even after a few months. These findings take on added significance in light of an ongoing Phase 2 clinical trial at the University of Arizona, where a team of researchers from the Department of Neurology is testing low-dose ketamine infusions as a treatment for dyskinesia in patients with Parkinson's disease.
Early results from this study seem promising, with some patients experiencing benefits that last for weeks after a single course of treatment. Ketamine doses can be modified to maintain therapeutic benefits with minimized side effects.
