Exercise Supports Stem Cell-Based Parkinson’s Therapy

Parkinson’s disease (PD) is a disabling neurodegenerative disease that affects approximately 10 million people worldwide, with numbers steadily increasing. Symptoms include tremors, difficulties with movement and speech, as well mental health issues and dementia. Although PD can be managed by medication and lifestyle adjustments, the efficacy of these interventions varies between patients and cannot stop or reverse disease progression.  

PD is caused by progressive loss of a certain type of neurons in the brain which produce dopamine, a chemical substance required to control movement, etc. Encouragingly, studies dating back to the eighties have shown that replacing lost dopaminergic neurons with donated fetal tissue-derived neurons can improve symptoms in PD patients. Since then, researchers have made progress in generating a replenishable source of dopaminergic neurons from pluripotent stem cells in the lab and achieved promising results when transplanting these cells in animal models of PD. Currently, clinical trials are ongoing to test the safety and efficacy of transplanting such stem cell-derived neurons in PD patients. A key to success in patients will be the successful integration and maturation of the transplanted cells within the brain. To address this, a research team led by Clare Parish from The Florey Institute of Neuroscience and Mental Health (in Melbourne) and Lachlan Thompson from the University of Sydney, Australia has now tested whether exercise enhances transplant function in PD rats. In their study, rats received a stem cell-derived transplant to replace lost dopaminergic neurons and some of the rats were given free access to a running wheel. Their work was recently published in Stem Cell Reports. While the neural grafts improved gross motor function, combined with exercise saw paw movements and agility improved significantly. Their research found that voluntary exercise improved the maturation of the transplant and the establishment of connections between the transplant and the rat neurons. A likely cause for this was the enhanced secretion of certain beneficial proteins in the brains of exercising rats which promoted transplant survival and integration. 

In conclusion, exercise may be a non-invasive and easily implemented strategy to enhance treatment outcomes in PD patients in combination with stem cell-derived transplants, warranting further testing in upcoming clinical trials.

Reference: Moriarty N, Fraser TD, Hunt CPJ, et al. Exercise promotes the functional integration of human stem cell-derived neural grafts in a rodent model of Parkinson’s disease. Stem Cell Reports. doi: 10.1016/j.stemcr.2025.102480

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