Podcast Episode 130: Meet the Researcher: Gene Silencing to Prevent and Treat Levodopa-Induced Dyskinesia

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Dyskinesia is a condition involving erratic, uncontrollable muscle movements such as twitches, jerks, twisting, or writhing of the face, arms, legs, or trunk. It can be a complication after long-term use of levodopa to treat Parkinson’s disease. Dyskinesias can be mild, or they may be severe enough to interfere with normal functioning.

Basic laboratory research has revealed some of the changes in the brain after long-term exposure to levodopa. In this episode, Kathy Steece-Collier, PhD, a professor in the Department of Translational Neuroscience in the Michigan State University College of Human Medicine in Grand Rapids, discusses her research into the biologic mechanisms of levodopa-induced dyskinesias and a possible future prevention and treatment for them.

Funded by an International Research Grant from the Parkinson’s Foundation, she delineated the role of calcium channels, which allow calcium to enter nerve cells in the brain, in the development of levodopa-induced dyskinesias. Based on those findings, she is now working on an approach that uses a single injection into a part of the brain that is affected in Parkinson’s disease (the striatum) that may have the potential for long-term prevention or relief of dyskinesias. The idea is to introduce a short piece of RNA with a tight hairpin turn in it, called a short hairpin RNA (shRNA), to silence the gene that leads to abnormal calcium channel signaling in the striatum that causes dyskinesia. Dr. Steece-Collier also explains how this technique may have advantages over drug therapy to control dyskinesia.

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About This Episode

Released: May 31, 2022


Kathy Steece-Collier, PhD

Kathy Steece-Collier, PhD is a Professor in the Department of Translational Neuroscience in the College of Human Medicine at Michigan State University. Over the past 20+ years, she has maintained her dedication to the development of improved therapeutics for individuals with PD with particular emphasis in understanding how, when the brain attempts to ‘fix itself’, aberrant remodeling of brain cells and their circuits results in the development of side-effects and/or lack of response to DA replacement therapies including levodopa medication and DA neuron grafting. By understanding how and why the brain changes in response to PD, her team hopes to find ways to prevent or repair the changes and improve therapeutic responses in individuals with this disease. Dr. Steece-Collier’s current research is focused on using a gene therapy approach that allows precise genetic silencing of a particular population of calcium channels, called CaV1.3 channels, to prevent aberrant ‘remodeling’ and reduce the often debilitating side-effect known as levodopa-induced dyskinesias in parkinsonian rats.

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