Long-term treatment for Parkinson’s disease often brings a troublesome side effect: involuntary, erratic movements that significantly impact patients’ quality of life. Known as Levodopa (L-DOPA)-induced dyskinesia, these motor complications have been a persistent challenge in managing Parkinson’s disease. However, recent research has shed light on a potential solution that could alleviate these debilitating effects, offering renewed hope for those affected by this chronic condition.

Researchers have made significant strides in addressing the motor complications associated with long-term treatment of Parkinson’s disease (PD). Led by Professor Heinz Steiner, Dr. Feras Altwal, Connor Moon, and Professor Anthony West from Rosalind Franklin University of Medicine and Science explored the effects of the multimodal serotonergic agent vilazodone on L-DOPA-induced gene regulation in striatal projection neurons and its potential to mitigate dyskinesia in an animal model of PD. Their findings were published in the journal Cells.

Parkinson’s disease, a neurodegenerative disorder characterized by the loss of dopamine-producing neurons, is often treated with L-DOPA. While L-DOPA remains the gold standard treatment, its long-term use can lead to L-DOPA-induced dyskinesia, a condition marked by involuntary, erratic movements. Dyskinesia significantly impairs the quality of life for patients with PD, as it complicates the therapeutic benefits of L-DOPA.

The research team investigated vilazodone, a drug approved by the U.S. Food and Drug Administration for its antidepressant properties, which combines selective serotonin reuptake inhibitor (SSRI) effects with partial agonist activity at the 5-HT1A receptor. Their study involved a well-established animal model of PD, where rats underwent unilateral dopamine depletion using 6-hydroxydopamine (6-OHDA). The rats were then treated with L-DOPA alone or in combination with vilazodone over three weeks.

“Our most important conclusion is that vilazodone effectively suppresses the development of L-DOPA-induced dyskinesia without interfering with L-DOPA’s beneficial motor effects,” said Professor Steiner. The researchers found that L-DOPA treatment significantly increased the expression of certain genes, such as dynorphin, 5-HT1B, and zif268 mRNA, in the striatum ipsilateral to the lesion. Vilazodone co-administration inhibited these neuronal effects, suggesting a targeted mechanism by which vilazodone mitigates dyskinesia.

The findings also highlighted that vilazodone’s influence was specific to the direct pathway of the dopamine-depleted striatum, as it did not affect enkephalin expression in the indirect pathway or gene expression in the intact striatum. This specificity could be crucial in developing adjunct therapies that offer symptomatic relief without compromising the primary treatment’s efficacy.

Professor Steiner noted, “These results position vilazodone as a potential adjunct medication for treating L-DOPA-induced motor side effects in Parkinson’s disease. The drug’s ability to modulate serotonin and dopamine systems could pave the way for new treatment strategies.”

In summary, the study by Professor Steiner and his colleagues demonstrates that vilazodone can effectively reduce L-DOPA-induced dyskinesia, a common and debilitating side effect in PD therapy, without impairing L-DOPA’s therapeutic efficacy. These promising results suggest that vilazodone, already approved as an antidepressant, could be repurposed to improve the quality of life for patients with PD undergoing L-DOPA treatment. Future research will focus on validating these findings in clinical trials that explore the long-term benefits of vilazodone as part of PD management.

Journal Reference

Altwal F., Moon C., West A.R., Steiner H. “The Multimodal Serotonergic Agent Vilazodone Inhibits L-DOPA-Induced Gene Regulation in Striatal Projection Neurons and Associated Dyskinesia in an Animal Model of Parkinson’s Disease.” Cells. 2020. DOI: https://doi.org/10.3390/cells9102265

About the Author

Dr. Heinz Steiner is a Full Professor of Cellular and Molecular Pharmacology at the Chicago Medical School, Rosalind Franklin University of Medicine and Science, and a Principal Investigator in the Stanson Toshok Center for Brain Function and Repair at Rosalind Franklin University. Dr. Steiner received his M.S. in Biology from the Swiss Federal Institute of Technology (ETH) in Zurich, Switzerland, and his Ph.D. in Physiological Psychology from the University of Dusseldorf, Germany. After post-doctoral work at the National Institute of Mental Health, Bethesda, he was a Research Assistant Professor in the Department of Anatomy and Neurobiology at the University of Tennessee, College of Medicine and The Center for Neuroscience in Memphis. He joined the faculty in the Department of Cellular and Molecular Pharmacology at the Chicago Medical School in 2000, and was department chair from 2011-2022. Dr. Steiner’s research focuses on the functional organization of the basal ganglia and related brain systems, especially on the role of the neurotransmitters dopamine and serotonin in the regulation of basal ganglia – cortical interactions. One of the main objectives of his work is to understand how treatments with dopaminergic and serotonergic drugs produce changes in gene regulation in the basal ganglia and their consequences for drug addiction and other brain disorders. Dr. Steiner is the senior editor of the “Handbook of Basal Ganglia Structure and Function” and a co-editor of Elsevier’s “Handbook of Behavioral Neuroscience” series.