Grant of $1 million awarded to develop new treatments for dyskinesia

Clinical study seeks to validate dyskinesia clinical scales, lowering hurdle to industry investment in new treatments

The Michael J. Fox Foundation for Parkinson's Research has awarded $1 million for a clinical study aiming to make a critical step toward the development of new treatments for dyskinesia, the excessive and uncontrollable movements that are a complication of long-term dopamine replacement therapy in patients with Parkinson's disease. The goal is to establish a framework for testing novel anti-dyskinesia treatments by validating clinical scales used to measure changes in dyskinesia severity.

Significant problems in measuring dyskinesia and assessing the efficacy of potential new therapies have created major roadblocks to clear-cut trial results and, therefore, industry investment leading to new and better interventions. The establishment of validated tools for use in dyskinesia clinical trials would significantly reduce the barrier for biotech and pharmaceutical companies to invest in trials to address this debilitating aspect of living with Parkinson's.

"Dyskinesia is a top priority for our Foundation because of its significant negative impact on patients' quality of life," said Katie Hood, Foundation CEO. "There is no therapy approved by the U.S. Food and Drug Administration (FDA) to treat it. Clinicians primarily prescribe one medication, amantadine. But amantadine works only for some patients and for a limited time and, in any case, its efficacy against dyskinesia requires rigorous scientific validation."

The study holds two primary aims: quantitatively establish the degree of changes in dyskinesia severity as a result of treatment with amantadine; and conclusively determine which scale or scales most accurately detect these changes. Patients will be treated with amantadine or placebo, and then have their dyskinesia rated over the course of several weeks using numerous dyskinesia measurement scales. The researchers will examine the response to placebo as well in order to favor scales that maximally separate placebo-associated changes from amantadine-associated changes. The results will establish a path for clinical testing of future promising novel dyskinesia treatments.

The double-blind, placebo-controlled trial, enrolling 66 PD patients at up to eight sites in the United States, Canada and Europe, will be led by coordinating principal investigators Christopher G. Goetz, MD, and Glenn T. Stebbins, PhD, of Rush University Medical Center in Chicago.

"Dyskinesia is a harrowing problem for people with Parkinson's disease," said Dr. Goetz, who divides his time between seeing PD patients in his clinical practice and conducting clinical research.

"The drug levodopa, which is converted to dopamine, the chemical lost in Parkinson's disease, is our gold-standard treatment for relieving stiffness, tremors and rigidity," said Dr. Goetz. "But patients are forced to weigh the symptomatic relief offered by levodopa against the knowledge that, at some point, it will very likely cause dyskinesia. So, many patients wait as long as possible to begin using levodopa, and even after starting the medicine, they limit the dosage to reduce the risk of dyskinesia. Those who develop dyskinesia often need to reduce their levodopa dose and therefore settle for a sub-optimal benefit from the best medical therapy available for their disease."

This project is being carried out on the recommendation of The Michael J. Fox Foundation's Dyskinesia Working Group, an international consortium of the world's top experts (including Dr. Goetz) in dyskinesia convened by MJFF to assess the state of therapeutic development in dyskinesia and make strategic recommendations for faster progress toward transformative treatments.