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By Mark Hirsch, PhD, and Mark Newman, PhD

No one knows exactly how exercise-based treatment enhances motor recovery in patients living with Parkinson’s disease (PD), but it has been widely suspected that brain-derived neurotrophic factor (BDNF) plays a key role. That’s why we completed the first meta-analytic study of neurotrophin release during exercise in people with PD – and confirmed that BDNF increases with exercise and may be responsible for improved brain function.

This discovery sheds new light on the mechanisms behind exercise-based treatments and opens the door to potential therapies that could boost BDNF and ameliorate symptoms of PD and other neurodegenerative diseases.

Increased BDNF Levels = Motor Skills Improvement

For the study, we collaborated with Erwin van Wegen, PhD, from Amsterdam University Medical Center and Patricia Heyn, FGSA, FACRM, from the University of Colorado’s Anschutz Medical Campus to investigate whether BDNF changes were consistent across human PD studies. Our meta-analysis pooled data from two randomized controlled trials on high-intensity exercise among PD inpatients and outpatients.

A total of 100 patients participated in these studies, including 52 ambulatory patients with mild to moderate idiopathic PD severity. These patients underwent a treatment regimen that included high-intensity, stationary cycling exercise and physical therapy.

We found that BDNF levels increased in these patients, and that these increases correlated with improved motor skills. In fact, our meta-analysis showed a significant heterogeneous summary effect size (mean difference of -5.53) improvement on the motor examination portion of the Unified Parkinson’s Disease Rating Scale. This exceeds the minimum clinically important difference and confirms that exercise affects the dopaminergic pathways. These findings were published in Translational Neurodegeneration.

Pursuing Therapies That Amplify BDNF

In short, we identified that exercise is a “volume control” that can “turn up” BDNF levels and potentially promote neuroplasticity. The next challenge is to develop a broader range of therapies to amplify BDNF levels in patients at all stages of PD. We are pursuing this at Carolinas Rehabilitation, by working to further illuminate the neurological mechanisms that explain how exercise benefits PD patients.

For example, we are participating in an international Amsterdam Movement Science Innovation planning grant to develop pilot studies that will further investigate the effect of exercise on neurotrophins.

World-Class Research Team

This critical work illustrates how Carolinas Rehabilitation does more than provide world-class clinical care – we also make seminal scientific contributions via translational laboratory research. Our physical medicine and rehabilitation research team includes renowned experts in brain injury, spinal cord injury, stroke, Parkinson’s disease and related neurodegenerative disorders.

These experts use a “neurons to neighborhoods” approach that starts with a bench science evaluation of what happens at the molecular level in a patient’s brain and continues to the bedside and beyond. For example, we also evaluate broader factors that may determine recovery from injury or trauma such as patients’ social networks and how their communities can support healing after hospital discharge.

It’s all part of how our researchers work to help patients recover physically, cognitively and psychosocially, so they can enjoy a better quality of life and get back to participating in their communities.

Read the paper in Translational Neurodegeneration.

To learn more, email Dr. Hirsch at or Dr. Newman at