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    Combination therapy treats symptoms of Parkinson's

    Benefit from each dose lessens over time.

    PARKINSON'S DISEASE is one of the most common neurologic disorders, affecting about 1.5 million people in the United States. Its major symptoms include slow movements, tremors, rigidity and impaired balance and coordination. These symptoms are attributed to the deterioration and loss of dopamine-producing nerve cells in the brain.

    Dopamine is a neurotransmitter involved in controlling movement and coordination. The principal medication used to control Parkinson's symptoms is levodopa, a precursor of dopamine, which is converted into dopamine when it reaches the brain. It is usually combined with carbidopa, which prevents or reduces potential side effects.

    "For the first two to five years of treatment, levodopa produces a sustained response, but as the disease progresses, the duration of benefit from each dose becomes shorter—the wearing-off effect," says Mark Abramowicz, MD, editor-in-chief of The Medical Letter on Drugs and Therapeutics, a non-profit newsletter that critically appraises drugs. "Still later, some patients develop sudden, unpredictable fluctuations between mobility and immobility—the 'on-off' effect. As the disease progresses, patients often develop levodopa-resistant motor problems including difficulties with balance, gait, speech and swallowing. Non-motor symptoms, including cognitive and psychiatric difficulties, become more prominent."

    In addition to levodopa, dopamine agonists are often used to reduce Parkinson's symptoms, particularly in the early stages of the disease. A dopamine agonist isn't changed into dopamine when it enters the body, but it directly stimulates receptors in nerves that would normally be stimulated by dopamine. Although dopamine agonists aren't as effective as levodopa in controlling motor symptoms, they do postpone the need for levodopa, and thereby delay the onset of abnormal muscle movements associated with long-term levodopa therapy.

    Symptomatic treatments allow most people to extend the period of time in which they can lead relatively normal, productive lives. However, currently there is no treatment that can reverse the progressive degeneration of neurons associated with Parkinson's disease.

    SLIGHT CHANGES AFFECT PATIENTS


    Some Drugs for Parkinson’s Disease
    Carbidopa/levodopa is available in generic form. About a year ago, because of a change in manufacturers, there was a temporary shortage of branded carbidopa/levodopa, and many people were transitioned to generics.

    "We run a helpline, and during this period we had several hundred phone calls from people who were very unhappy about the changes," recalls Peter N. Schmidt, chief information officer of the National Parkinson Foundation.

    The shortage is over now, and helpline calls are back to normal levels.

    "In Parkinson's disease you don't want to change medications. This is a disease where the placebo effect is tremendous, and any confusion or change can have a significant negative effect on patients," says Schmidt.

    There is some evidence of slight differences among generics and branded formulations of levodopa, and some patients experience real changes in outcomes on switching.

    "It's not clear whether these changes reflect different drug dynamics or simply a worsening of symptoms due to concern about a perceived change. Either way, the response results in worse outcomes and higher utilization of care, and so for these patients it's important not to switch them from one formulation to another, even though they may theoretically be equivalent," he says.

    "While there is a classic symptomology of Parkinson's disease, in each person the disease is somewhat different. We might usefully think of it as a disease spectrum," says Beth-Anne Sieber, program director at the National Institute of Neurological Disorders and Stroke.

    "Now researchers understand the disease well enough to work on developing medications that will hopefully stop the progression of the disorder," she says.

    One promising approach is CERE-120, a form of gene therapy that uses neurotrophic factors to increase the health and function of dopamine neurons. CERE-120 recently completed enrollment in a clinical trial.

    "Many approaches are moving forward, but it will be several more years before they reach consumers," she says. "Because of the complexity of the disease, it may take a combination of therapies to help stop disease progression."

    Surprisingly the most promising treatment in Parkinson's disease is exercise, according to Schmidt. A number of animal models that have shown that exercise has a dramatic benefit.

    "We've known for a long time that exercise helps with symptoms, but now we're starting to think that exercise could help slow the progression of the disease," he says.

    This research looked at intense, vigorous exercise. There are two different schools of thought on why this matters for Parkinson's, Schmidt says.

    "One school thinks you have the mechanical benefit of fluids flowing and blood moving," he says. "Another school thinks that serious physical training, beyond your comfort level, creates a signal for your brain to grow and learn."

    Elaine Zablocki has been covering healthcare for 20 years.

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