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

Substantial Matters: Life & Science of Parkinson’s

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.