What if certain parts of the brain could be turned off to treat neurological disorders like Parkinson’s disease? Though it seems far-fetched now, such a solution could soon become reality.
During the last 10 years, the field of neuroscience research has been revolutionized by new genetic techniques, allowing neuroscientists to express artificial proteins in neurons that can then be modified to study diseases and disorders. One of the most commonly used genetic-based approaches is called chemogenetics.
Chemogenetic techniques use artificial receptor proteins that only become active in the presence of a specific drug. This means only the neurons containing the artificial receptor will change their activity in response to the drug, while other neurons remain unaffected. We can think of it as a chemical switch that turns specific neurons on or off.
While chemogenetics methods have been extensively used in basic research, they have yet to be translated to clinical treatment. However, researchers have recently developed new chemogenetic tools that have the potential to be used in clinical applications. The team, led by Scott Sternson (Howard Hughes Medical Institute’s Janelia Research Campus), included Yerkes National Primate Research Center researchers Adriana Galvan, PhD, and Xing Hu, MD.
In this new chemogenetic system, the researchers activated the artificial receptors by using drugs specifically designed for the receptors, as well as varenicline (Chantix™), an antismoking drug. The receptors and drugs were optimized during in vitro experiments and then successfully used to control the activity of neurons in rodents.
The Yerkes researchers then contributed an important step toward potential clinical application of the tools by duplicating the effects in a nonhuman primate’s brain. When the primate received a low dose of varenicline, the neurons containing the artificial receptors were silenced — all with no observable side effects. The results provide a critical proof of concept that chemogenetic methods can be effectively used in nonhuman primate studies.
Yerkes researchers are now expanding the chemogenetic experiments with the aim of using them in a nonhuman primate model of Parkinson’s disease, which is characterized by some movement-related brain regions being abnormally active. Chemogenetic manipulation could potentially silence or at least modulate the activity of these brain areas and help scientists develop a novel Parkinson’s therapy.
