Drug Research Targets Parkinson's Disease

Nearly 1.5 million people in the US have already been diagnosed with Parkinson's disease, and about 50,000 new cases are reported annually. Both prevalence and incidence of Parkinson's disease increase with advancing age; the rates are very low in people under 40 and rise among people in their 70s and 80s. (The average age of onset is about 60.)

It's no surprise, then - especially considering the increasing average age of the US population - that studies of new Parkinson's drugs and new methods of delivering existing medications are expanding.

"Parkinson's disease is a neurological disorder that affects one's coordination and ability to move, and it often is accompanied by tremor," said Karen A. Blindauer, MD, Medical College Assistant Professor of Neurology and Director of the Movement Disorders Clinic.

Dr. Blindauer is part of the national Parkinson's Study Group and has been co-principal investigator in two major Parkinson's research studies; she also participates in ongoing research at the Medical College of Wisconsin. In addition Dr. Blindauer teaches the basic neurology/movement disorders lectures for Medical College students and residents and teaches hospital courses on the diagnosis and treatment of movement disorders.

Parkinson's disease occurs when the neurons that produce the neurotransmitter dopamine die or become impaired. Without sufficient dopamine to properly transmit the nerve impulses, the wrong neurons can fire out of control. As control over the delivery of nerve messages is diminished, so is control over movement.

The four primary symptoms of Parkinson's are tremor or trembling in hands, arms, legs, jaw, and face; rigidity or stiffness of the limbs and trunk; slowness of movement (bradykinesia); and impaired balance. Patients might have difficulty walking, talking or completing simple tasks.

Current Treatments Reduce Symptoms
No drug can stop the progression of Parkinson's disease, but a variety of medications provide dramatic relief from the symptoms and allow many patients to function very well.

"Most of the drugs that are available for Parkinson's disease are geared toward either increasing brain levels of dopamine or providing dopamine agonists, which are chemicals that mimic dopamine," said Dr. Blindauer. "The result is that it helps to decrease the stiffness or rigidity, to lessen tremors, and to reduce slowness and improve mobility."

Levodopa (L-dopa) is the most widely used agent for Parkinson's disease symptoms. Nerve cells can use levodopa to make dopamine and replenish the brain's diminished supply. Adding carbidopa prevents levodopa from being metabolized in the gut, liver and other tissues. This allows more levodopa to get to the brain so a smaller dose is needed to treat symptoms. In addition, the nausea and vomiting often associated with levodopa treatment is reduced.

For many patients, however, after 4 to 6 years of therapy, there is an ever-shortening duration of response to Levodopa. Entacapone can then be used to provide levodopa to the brain for longer periods of time. Entacapone, too, allows more levodopa to reach the brain, where it has its effects.

Combination drugs include Sinemet, made of levodopa and carbidopa, which has been commonly used for Parkinson's disease for more than 30 years; and Stalevo, a more recently approved product which contains levodopa, carbidopa, and entacapone.

Other drugs used to treat the symptoms of Parkinson's disease include the dopamine agonists such as ropinirole, pramipexole, and pergolide and other agents such as selegiline and amantadine. For patients whose symptoms cannot be optimally managed with medications, there are various surgical treatments for Parkinson's Disease.

PRECEPT Study Explores Investigational Drug
The Medical College of Wisconsin is participating in the Parkinson Study Group multi-center study called PRECEPT (Parkinson Research Examination of CEP-1347 Trial). PRECEPT is designed to evaluate the safety and effectiveness of a possible neuro-protective agent designed with the intent to delay the progression of Parkinson's disease.

"The PRECEPT study is investigating whether or not the investigational drug CEP-1347 can delay progression of the disease," said Dr. Blindauer. "Most of the drugs that are available today treat the symptoms but they do not delay the dying off of the nerve cells which leads to the progression of Parkinson's disease over time."

"This study has included people over age 30 at the very earliest point in their disease." Roughly 800 patients who are not taking any other Parkinson's disease medications have been enrolled in the study, at 65 Parkinson Study Group Centers across the United States and Canada. The study will run for two years; enrollment was completed in March of 2004.

Other Parkinson's disease drug administration approaches still in research stages and not yet approved by the FDA include transdermal patches and delivery devices implanted under the skin. Regardless of how medications are administered, the complexities of brain function and differences in how Parkinson's disease affects each individual will continue to drive research in the future.

Dan Ullrich
HealthLink Contributing Writer

For more information on this topic, see the HealthLink articles Medical College Movement Disorders Program and The Facts about Parkinson's Disease.

MCW Health News presents up-to-date information on patient care and medical research by the physicians of the Medical College of Wisconsin.