Exercise to Erase Symptoms

A new study aims to prove exercise can help reverse symptoms of Parkinson’s disease

By Beth Puliti
August 14, 2007
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During the early stages of Parkinson’s disease (PD), symptoms are mild and typically restricted to one side of the body. Rest tremor—the most common indication of the disease and perhaps the least disabling—can be the most embarrassing to the patient.1

But over time, patients with PD can exhibit more severe tremors, slowness of movement, stiffness, difficulty with balance, cramped handwriting, shuffling walk, muffled speech and depression.2

What if exercise could reverse these symptoms? It just might, say researchers of a cutting-edge study that appeared in the Journal of Neuroscience.

‘A Change in the Brain’
Approximately 60,000 new cases of Parkinson’s disease are diagnosed each year, affecting men and women in almost equal numbers. Currently, there are 1.5 millions people in the U.S. living with PD.2

Determined to help find a cure for the brain disorder, Michel Jakowec, PhD, and Beth E. Fisher, PhD, PT, along with others, set out to determine whether high-intensity, high challenge exercise in patients with PD would improve motor performance, and if this improvement could be in part explained by some change in the brain.

The study uses treadmill exercise in animal models. “One advantage of research in PD is that we have several excellent animal models of the disorder,” said Dr. Jakowec, assistant professor at University of Southern California.

MPTP—a contaminant produced by heroin addicts who made their own homemade drugs in the early 1980s—is used in the lab. “Self-administration of this contaminant by intravenous injection resulted in a form or Parkinson’s disease that emerged within days rather then years, and the clinical features were indistinguishable between these two forms,” explained Dr. Jakowec.

Identifying the contaminant as MPTP was a major breakthrough since administration of MPTP to mice and monkeys creates an animal model with many of the same features seen in humans with PD, he noted.

For one hour per day the mice involved in this study undergo intensive treadmill exercise on a motorized treadmill at a high speed of 20 meters per minute. Twenty-eight days of exercise are interspersed with weekends off for relaxation.

“We initially thought that if we subjected our Parkinsonian mice (which had features like humans with PD, including slowness) to an intensive exercise program, we would be able to see some benefit. Our thought at the time was that exercise would accelerate some of the natural ability of the brain to repair itself, similar to what is seen in early development,” said Dr. Jakowec. “To our surprise we discovered that the Parkinsonian brain (which is a state of injury) in fact finds new ways for surviving cells to work differently.”

The Role of Dopamine
Parkinson’s disease develops when neurons that manufacture dopamine die or become impaired in part of the brain known as the substantia nigra. According to the National Parkinson Foundation, when approximately 80 percent of these cells are damaged, symptoms of Parkinson’s disease appear.2

“It is unknown why these dopamine producing cells begin to die,” said Dr. Fisher associate professor of clinical physical therapy at University of Southern California. Dopamine, a critical chemical that allows effortless, coordinated muscle and movement function, controls other functions, such as cognition, motor activity, motivation, sleep, mood, attention and learning, she mentioned.

If it can be discovered how to kick-start these neurons and make them function more efficiently, the clinical features of PD may be able to be reversed.

“Even a small change may have great benefit,” Dr. Jakowec said. “Our studies show that intensive exercise can alter how the remaining dopamine-producing cells work and this can translate into improvement in motor behavior.

“Also, we found that by using electrophysiological techniques, surviving dopaminergic neurons alter the amount of dopamine they release. In fact, this increased release of dopamine is in response to the exercise program they are involved with,” he added.

Human Exercise Trials
Certain modifications to treadmill exercises used with animal models will need to be made for the Parkinson’s population. However, that is an easy task, said Dr. Fisher.

“We truly have a translational research model—findings from the mouse led to explorations in the human exercise trials and vice-versa,” she said.

Patients with PD are involved in treadmill exercise using body-weight supported systems. In the preliminary human high intensity body weight-supported treadmill trial (compared to low intensity exercise), the researchers found positive changes in motor performance and brain changes using Transcranial Magnetic Stimulation.

From what the researchers learn from these studies, they may be able to guide patients in other exercise regimens.

“Treadmill running and wheel running in rodents is an intensive motor task. For patients, the goal is to replicate such an intensive regimen that targets the motor system. If motor behavior is affected in disease, then treadmill running, jogging and swimming may be most beneficial,” said Dr. Jakowec.

Optimizing drug treatment with specific exercise programs may play a major role in altering disease progression and patients’ quality of life, noted Dr. Jakowec.

The development of the exercise regimen used in the study is the result of a lot of thought from Dr. Fisher and others in the Department of Biokinesiology whose interests focus on developing effective intervention for brain injury and disease, he said.

With regard to the PD population avoiding certain types of exercises, Dr. Fisher stated, “Fatigue is sometimes a symptom of PD and more specifically exercise-induced fatigue. It would be important to monitor individuals for this but continue to progress.”

Dr. Jakowec did not believe any exercise would be detrimental to patients with PD except those that may be life-threatening. “We hope that our studies, in conjunction with traditional symptomatic treatment, can be tailored to patients at any stage of the disease,” he said.

The Benefits of Exercise
PD has been considered a downhill process and not one that is amenable to activity-dependent neuroplasticity, noted Dr. Fisher. “We have evidence in the mouse model and some preliminary evidence in humans that this may not be the case. Physical therapy intervention may modify the disease process itself.”

This debilitating degenerative disorder currently has no cure. “We need a cure,” stressed Dr. Jakowec. “Also, whatever we learn regarding the mechanisms and benefits of exercise in the injured brain will have an impact on a wide range of disorders, including Alzheimer’s disease, brain injury, stroke and developmental disorders such as autism and aging.”

Other than proving the disease modifying effects of exercise, the researchers hope this study will change how challenging PT is for individuals with PD as well.

“We want people with early PD to begin to be referred to PT immediately upon diagnosis by their physicians. Currently this group of patients does not receive PT because they are relatively high level,” said Dr. Fisher.

Most of the researchers involved in the study now exercise a lot more, Dr. Jakowec admitted.

“Exercise can be neuroprotective and disease modifying and is beneficial at all stages of life, whether affected by a brain disorder or not. But we need to know the mechanisms that take place in the brain to help us improve the effects of exercise and to understand the diseases we are confronted by,” he said.

“I am training for a marathon and so is my colleague and wife, Dr. Giselle Petzinger. Many patients continue to exercise and newly diagnosed patients now take up exercise as a regular part of their daily regimen.”

References
1. National Parkinson Foundation. (2007). Parkinson Primer. Retrieved from the World Wide Web, http://www.parkinson.org/

2. National Parkinson Foundation. (2007). About Parkinson Disease. Retrieved from the World Wide Web, http://www.parkinson.org/