Study shows new drug reduces advanced Parkinson's disease symptoms

August 12, 2003

Tampa, FL (August 13, 2003) -- After 40 years of treating Parkinson's disease with dopamine medications, a new study shows potential for a non-dopamine drug that may provide benefit for patients with advanced Parkinson's disease.

Robert A. Hauser, M.D., first author of the study and director of the Parkinson's Disease and Movement Disorders Center at the University of South Florida, and other researchers across the United States, found istradefylline (KW-6002) reduced by 1.7 hours per day the time that advanced Parkinson's disease patients experienced tremors, slowness and stiffness. Istradefylline did not worsen the severity of dyskinesias and was generally well tolerated by participants.

The study, sponsored by Kyowa Pharmaceuticals, Inc., appears in the August 13, 2003, issue of the journal Neurology.

Patients with Parkinson's disease have less control over motor function and experience worsening tremors, slowness and stiffness as the disease advances. Current dopamine replacement therapy improves those symptoms, but after several years the treatment becomes complicated by a shortened duration of benefit and the emergence of twisting, turning movements called dyskinesias. Once this occurs, increasing dopamine medication worsens dyskinesias and reducing dopamine medication allows a worsening of slowness, stiffness, and tremors.

"Once patients with Parkinson's disease develop both motor fluctuations and dyskinesias, it is very difficult to provide further benefit with dopamine medications," said Dr. Hauser. "This study opens the door to the possibility of providing additional benefit for advanced Parkinson's disease patients and confirms the idea that medications that affect neurotransmitters other than dopamine can provide benefit in Parkinson's disease."

In this 12-week, double-blind, placebo-controlled study, 83 patients with motor fluctuations and dyskinesias on levodopa (a dopamine medication) were randomized to three groups. All participants continued their levodopa treatment. One group additionally received placebo, another up to 20 mg per day of istradefylline, and the last up to 40 mg per day of istradefylline.

Participants noted their status--whether they were asleep, OFF (medication benefit having worn off), ON (medication providing benefit) without dyskinesia or ON with dyskinesia--during half-hour intervals three times a week on home diaries.

Earlier studies in animal models of PD showed istradefylline exerts an antiparkinsonian effect without worsening dyskinesia. Istradefylline, an adenosine A2A receptor antagonist, changes the firing of neurons in a way that improves motor function in Parkinson's disease.

"More work is needed," Dr. Hauser said. "We may be able to reduce the time patients are OFF with slowness, stiffness, and tremors without worsening the severity of dyskinesias. With dopamine medications alone, this is difficult to do."
Other investigators for this study were Jean P. Hubble, MD, of the Ohio State University Department of Neurology, Columbus, OH; Daniel D. Truong, MD, of the Parkinson's and Movement Disorder Institute, Fountain Valley, CA; and the Istradefylline US-001 Study Group.

Drs. Hauser and Hubble received compensation from Kyowa for consultation related to the design and implementation of future studies.

University of South Florida (USF Health)

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