Researchers at the University of Arizona have uncovered new insight into one of the most common complications faced by Parkinson's disease patients: uncontrolled movements that occur after years of treatment.
Parkinson's disease – a neurological brain disorder that affects a person's movements – develops when levels of dopamine, a chemical in the brain responsible for body movements, begin 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 uncontrolled 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, may help address this complex condition.
Over the years, a Parkinson's patient's brain adapts to levodopa treatment, which is why levodopa causes dyskinesia in the long term. In a new study, the research team found that the motor cortex - the area of the brain responsible for controlling movement - becomes effectively "switched off" during dyskinetic episodes.
Studies have shown that ketamine can help disrupt the abnormal repetitive electrical patterns in the brain that occur during dyskinesia. This could potentially help the motor cortex regain control of movement.
Ketamine works in two stages in these patients. First, it disrupts these abnormal electrical circuits that occur during dyskinesia. Then, hours or days later, ketamine triggers a much slower process that allows brain cell connectivity and activity to change 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 several months. These findings take on added significance in light of a Phase 2 clinical trial underway 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 appear promising, with some patients experiencing benefits that last for weeks after a single course of treatment. Ketamine doses can be adjusted to maintain therapeutic benefits with minimized side effects.
