SYDNEY—Physical therapy interventions could provide significant benefits for patients with Parkinson’s disease, according to a review of clinical trials in movement disorders presented at the 17th International Congress of Parkinson’s Disease and Movement Disorders. In contrast, many pharmacologic treatments have failed to show benefits in clinical trials conducted during the past year.
Many recent studies have evaluated physical therapy interventions such as exercise therapies. “The largest area of research really is in physical exercise and activity,” said Susan H. Fox, MRCP, PhD, Associate Professor of Neurology at the University of Toronto. At least 12 randomized controlled trials have been conducted during the past 12 months, she added.
An analysis conducted according to the Movement Disorder Society’s evidence-based review protocols concluded that physical therapies are likely efficacious and clinically useful, said Dr. Fox. A Cochran review meta-analysis of trials that compared physiotherapy with no intervention found that physiotherapy provided a significant benefit, as measured by the Unified Parkinson’s Disease Rating Scale Part III.
Approximately 2,000 subjects participated in the trials that were reviewed. The investigators found no difference between the types of therapy, said Dr. Fox. “Exercise is showing a benefit, but we don’t know which type is going to be better than any other,” she added.
The design of trials evaluating physical therapy has improved over time, Dr. Fox pointed out, but the trials still present the following unique challenges:
• Inability to blind patients to the intervention
• Potentially inappropriate control groups
• Nonequivalence of supervised versus unsupervised exercise
• Heterogeneity of types and frequency of exercise across trials
• Lack of comparative end points.
Another challenge is to persuade patients with Parkinson’s disease to exercise. These patients are generally much more sedentary than age-matched controls, said Dr. Fox. One study conducted in the Netherlands called Park-Fit was designed to encourage activity in patients with Parkinson’s disease through an intervention that involved walking around, going to stores, and performing simple daily exercises. The researchers used a physical activity questionnaire to record the type and frequency of patients’ activity during the previous week. The questionnaire also was validated with a pedometer. The trial did not reach its end point.
“Exercise is very different from taking a tablet,” said Dr. Fox. “You have to remember that in these patients. They have apathy and mood disorders, so encouraging them about this is much harder.”
During the past year, many trials of medicines for Parkinson’s disease yielded disappointing or negative results, said Dr. Fox. Trials that examined therapies’ disease-modifying or neuroprotective effects were largely negative. In particular, trials of drugs that target the glial cell-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor system have consistently failed. The reason may be that Parkinson’s disease reduces the number of GDNF receptors in the brain, thus limiting these drugs’ ability to act, said Dr. Fox.
A phase III trial of the adenosine A2A antagonist preladenant as monotherapy failed to show significant benefit, according to Merck & Co. As a result, the company suspended further investigation of the drug.
—Linda Peckel
Contributing Writer