Parkinson's Disease: The Cutting Edge

Last Editorial Review: 3/17/2005

Experts explain how new research and new drugs offer Parkinson's disease patients more options than ever -- and exciting new treatments to come. 

By Colette Bouchez
WebMD Feature

Reviewed By Brunilda Nazario

Some famous faces have recently focused our attention on the progressive neurological disease known as Parkinson's disease. Most notable among them are Pope John Paul II, actor Michael J. Fox, and former Attorney General Janet Reno.

But now, doctors say some cutting-edge treatments may soon take center stage. Among the new discoveries: a transdermal skin patch for round-the-clock symptom control; two new surgical procedures for treating advanced disease; and a brand new way of diagnosing Parkinson's disease long before the movement disorder begins to show its signs.

"It's vital for patients and their families to know that we are moving forward every day, and every day we are learning more about this illness," says Michael Kaplitt, MD, PhD, director of Movement Disorders Surgery at Weill Cornell Medical Center/New York Presbyterian Hospital in New York City.

A progressive neurological disease affecting some 500,000 Americans, Parkinson's disease involves the early death of nerve cells that manufacture dopamine. This is a chemical transmitter that stimulates muscles to move in a smooth and coordinated way.

When levels of dopamine are depleted, other brain chemicals become dominant, causing an imbalance that further encourages a lack of muscle control, or sometimes a rigidity that prevents muscle movement. The symptoms can sometimes be felt body-wide.

"In the beginning this can include mild problems, such as a sense of fatigue and restlessness accompanied by small tremors in the hands, arms, and feet; as the disease progresses a patient will have difficulties orchestrating movement in all muscle groups, which can affect walking and even speaking," Kaplitt tells WebMD.

Kaplitt says that by the time symptoms appear, over 70% of the dopamine-producing cells are no longer working, making reversal of the disease impossible.

"It would be safe to say that basically all of our treatments right now are focused on relieving symptoms and not restoring brain function," says Roger Albin, MD, professor of neurology at the University of Michigan and chief of neuroscience research at the Ann Arbor Veterans Affairs Medical Center.

But Albin says many of the newest treatments can dramatically alter the quality of life and even help people who suffer from Parkinson's live longer.

For many years, the only treatment Parkinson's patients could rely on were medications designed to help the brain produce more dopamine, act like dopamine, or reduce the breakdown of dopamine within brain cells. While the drugs are effective, many have troubling side effects, including offering only sporadic muscle control. Most, say experts, lose their effectiveness as the disease progresses.

Now, doctors say there is a way to overcome many of these problems with the addition of a cutting-edge treatment known as deep brain stimulation (DBS). It is used only in people whose symptoms cannot be controlled adequately with medication. Doctors use waves of electrical current to affect the way brain cells communicate, and in doing so can help a number of Parkinson's medications work far more effectively for much longer periods of time.

The treatment inactivates regions of the brain that cause tremor and Parkinson's disease symptoms, thereby blocking abnormal nerve signals.

"By sending small pulses of electrical stimulation into the brain we can create a kind of 'noise' that dampens down the flow of abnormal information between brain cells," says Kaplitt. Ultimately, it helps rebalance some of the brain chemistry involved in movement, allowing medications to work better and more effectively.

The treatment itself involves surgery during which an electrode is implanted into the area of the brain where dopamine is made. That electrode is attached to lead wires buried under the skin and connected to a source of electricity outside the body.

"We can then turn it up or down and adjust the flow of 'noise' to suit every patient's individual needs and the stages of disease," says Kaplitt.

Although in research for about nine years, Kaplitt says DBS has only recently stepped into the limelight as an effective treatment and that many Parkinson's patients are still not aware of just how helpful it can be.

Because the surgery is done primarily to increase the effectiveness of current medications, those already responding well to drug therapy are not candidates.

For those who are able to find relief with drug therapy, there may soon be a new treatment option as well. In March 2005, Aderis Pharmaceuticals and Schwarz Pharma applied to the FDA for approval of Rotigotine CDS, the first once-daily transdermal skin patch designed to deliver a steady flow of a dopamine-like replacement drug, which may offer better muscle control.

In what may soon prove to be the Parkinson's treatment the world is waiting for, doctors have exciting new hope for gene therapy and the ability to reprogram brain cells to overcome dopamine loss.

As Kaplitt tells WebMD, in this approach, a harmless virus is used to carry a "package" of genetic material directly into brain cells. Once there, he says the package unfolds and begins to "reprogram" those cells, enabling them to begin manufacturing the missing chemicals. Eventually, says Kaplitt, the virus that delivered the package burns itself out, leaving no ill effects on the body. The end result: brain cells that function closer to normal.

Kaplitt is heading up the first study ever to use gene therapy on the brain of a human adult for something other than cancer. Thus far, he says, "surgery on nine patients has yielded promising results."

Kaplitt and his team are expected to release further information about their results at next month's meeting of the American Association of Neurological Surgeons in New Orleans.

In the meantime, however, many questions still remain. Among them: Whether the results thus far can be duplicated on larger groups of patients. Some experts remain dubious of the possibility.

"It's a clever idea, but whether or not it turns out to be a good clever idea remains to be seen. It's an interesting experiment, let me say that," Albin tells WebMD.

Encouraging a "wait-and-see" approach, he points out that other therapies once showing great promise, like fetal tissue implanted into the brain, turned out to offer little in the way of actual help.

More recently, another promising treatment has met with disappointing results as well. Although recent studies showed that infusing the brain with a nerve growth factor known as GDNF may have some positive effects on some patients, Amigen, the company sponsoring the GDNF studies, recently announced it is going back to the lab for further research.

Though treating symptoms may be the most effective way to control an illness, as with most diseases, the Holy Grail of Parkinson's disease is to find a cure. An even greater goal: to discover how to prevent it from occurring at all. And it is in this area where one of the most intriguing cutting-edge possibilities exists.

Indeed, some of the latest research shows that though Parkinson's ultimately affects the brain, the very earliest signs of this disease may be present in an entirely different part of the body -- the heart.

"We are talking about damage occurring in the neurons [cells] that enervate the heart -- the cables that send the signals to the heart, particularly the left ventricle, which are not only affected by Parkinson's, they are affected very early on, perhaps even before the motor symptoms become an issue," says Horacio Kaufmann, MD, the Aidekman Professor of Neurology at the Mount Sinai School of Medicine in New York City.

As Kaufmann explains, defects similar to what occur in dopamine brain cells also occurs in cells that manufacture epinephrine in the heart -- the chemical that helps regulate heart rhythm and the strength of your heartbeat. And those changes, he says, seem to occur long before the symptoms in the brain begin.

What makes this discovery so exciting, he says, is "there are imaging studies that can map with some degree of accuracy this early defect in the heart cells."

In studies published in the journal Neurology in 2001, doctors hinted that early signs of Parkinson's may also be present in cells in the intestines, noting that chronic constipation may be an early marker of Parkinson's.

Kaufmann says he's not sure if his findings represent a true marker or if the problems within heart cells are simply responsible for some of the symptoms associated with the disease, like fatigue. What he's more sure of, however, is that focusing on the heart could allow doctors to identify problems in the brains of Parkinson's patients far earlier than is currently the case.

It may then be possible to take steps to stop the initial breakdown in the brain before movement is seriously impaired, he tells WebMD.

While identifying those at risk may be helpful, doing so may turn out to be more complicated than once thought. Although studies released by the National Institutes of Health in January noted the discovery of two new genes linked to the most common form of Parkinson's disease, a new cutting-edge theory says there may be far more forms of this disease than anyone realizes.

"Parkinson's disease is very different in that people can come in with a set of symptoms ... but whether or not everyone who has these symptoms actually has the same disease is now open to great question," says Steven Finkbeiner, MD, PhD, assistant professor of neurology and physiology at the University of California at San Francisco and an investigator at the Gladstone Institute for Neurological Disease.

While the end result may be the same, he says, the underlying causes may be vastly different, and that may mean that very different treatment approaches are needed to affect symptoms.

"Even in inherited forms of this disease differing pathways are involved, and that raises the possibility that there may be multiple causes, and that means there may never be a single targeted drug treatment for this disease," Finkbeiner tells WebMD.

Knowing this, however, may force scientists to think out of the box, he says, and look to other directions for helpful treatments. And that may be the future of Parkinson's research.

Published March 16, 2005.

SOURCES: Michael Kaplitt, MD, PhD, director of movement disorders surgery, Weill Cornell Medical Center/New York Presbyterian Hospital, New York. Roger Albin, MD, professor of neurology, University of Michigan; chief of neuroscience research, Ann Arbor Veterans Affairs Medical Center. Horacio Kaufmann, MD, Aidekman Professor of Neurology, Mount Sinai School of Medicine, New York. Steven Finkbeiner, MD, PhD, assistant professor of neurology and physiology, University of California, San Francisco; investigator, Gladstone Institute for Neurological Disease. Neurology, September 2004 -63:1093-1095. Neurology, Aug. 14, 2001; vol 57: pp 456-462. BioWorld Today, Feb 14, 2005. National Institute of Neurological Disorders and Stroke web site.

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