Ketamine for Parkinson's? Clinical trial in the works

July 20, 2018   By Maria Cohut

Researchers are planning a phase I clinical trial to test the dyskinesia-relieving effects of ketamine.

The drug used to manage some of the most salient symptoms of Parkinson's disease is known to expose patients to more motor issues, as part of its side effects. Researchers suggest that ketamine could be used to neutralize those side effects.

Parkinson's disease, a motor system disorder, is characterized by tremor, limb stiffness, impaired balance, and slowness of movement, as well as impaired movement coordination.

There is currently no known cure for this disorder, so treatments focus largely on managing the symptoms.

This helps people maintain autonomy and quality of life, as much as possible.

One of the main drugs used to treat Parkinson's disease is levodopa, which can help with limb stiffness and slowness of movement. But there is a caveat: patients for whom levodopa does work begin to experience potentially debilitating side effects after a few years on the drug.

"The problem is levodopa works great for a few years — we call that the 'honeymoon' period — but then you start getting these side effects," notes Dr. Scott Sherman, a neurologist at the University of Arizona College of Medicine in Tucson.

So what happens to many patients who take levodopa? They develop dyskinesia, or involuntary and uncontrollable movements that can affect the limbs, the head, or even the entire body, to various degrees of severity.

Once an individual develops levodopa-related dyskinesia, it does not go away unless treatment with this drug is discontinued altogether — though this may mean that their symptoms will no longer be managed.

But is there anything that could counteract levodopa's side effects? Dr. Sherman and colleague Torsten Falk believe that the answer may lie with ketamine.

Ketamine's effect on dyskinesia

Dr. Sherman and Falk found the first clues about ketamine's potential in offsetting dyskinesia when they tested it as a pain-relieving drug for patients with Parkinson's.

Their trial led them to observe an unintended yet welcome effect: dyskinesia was ameliorated, or even disappeared completely for a few weeks in the case of individuals on levodopa who were also administered ketamine.

When the researchers tried to duplicate these findings in a rat model, they found that the dyskinesia-offsetting effects of ketamine held strong.

This has led them to plan a controlled clinical trial in the hopes of discovering how — or whether — ketamine might best be used in conjunction with levodopa to treat patients with Parkinson's disease.

Ketamine's best-known side effect is dissociation (also known as disassociation), in which a person feels as though they are perceiving the world from some place outside of their own bodies. This uncanny effect is also why ketamine has notoriously been misused as a "party drug."

"Disassociation is a sort of 'out-of-body' experience. When people describe it, they have told me that they feel like they are in fish bowl," explains Dr. Sherman.

Another common risk of taking ketamine is raised blood pressure. However, the scientists are strategizing to keep these possible effects in check by carefully calculating dosage.

According to Dr. Sherman, "We are going to monitor blood pressure closely to make sure it doesn't get high. And," he continues, "we know at what dosage ketamine causes this disassociation; we expect that the dosage needed in Parkinson's disease will stay well below that level."

Upcoming clinical trials to confirm effects

The scientists plan to launch the phase I clinical trial — in which they will work with 10 patients with Parkinson's disease — later this year at the University of Arizona College of Medicine.

The project would be funded by a 3-year grant of $750,000, which will be awarded by the Arizona Biomedical Research Commission.

These funds are also due to cover additional experiments on a rodent model, which will allow the researchers to gain a better understanding of the underlying mechanisms at play.

"We want to find out exactly what ketamine is doing to have this effect," says Dr. Sherman.

"Ketamine has been long overlooked. Now it could prove very useful for Parkinson's patients."

Dr. Scott Sherman

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