Scientists at WashU Medicine have utilized the body’s internal circadian rhythm to administer medication for an inflammatory condition exactly when it is most required. Tissue implants that included genetically modified stem cells autonomously provided anti-inflammatory drugs to mouse models of rheumatoid arthritis on a daily basis just before the inflammation reached its peak. The researchers referred to this method as “chronogenetics.”

The findings were published on February 7 in Nature Communications.

Inflammatory episodes in rheumatoid arthritis are activated by variations in the concentrations of infection-fighting proteins within the body. The amounts of these proteins fluctuate throughout the day, governed by circadian cues associated with our typical 24-hour light-dark cycle. A group led by Farshid Guilak, the Mildred B. Simon Research Professor of Orthopaedic Surgery at WashU Medicine, created a specialized stem cell implant that contained a synthetic gene circuit designed to activate and discharge anti-inflammatory medication when the circadian signal was initiated.

The therapeutic implants, comprised of the reprogrammed stem cells integrated into cartilage structures, successfully managed inflammatory flare-ups in mice for as long as a month. The implanted gene switches also proved flexible: when the mice’s sleep cycles were altered from daytime to nighttime sleeping, the cells quickly readjusted to the new circadian rhythm.

In humans suffering from rheumatoid arthritis, painful inflammation caused by the body’s daily cycles might arise at 3 a.m., complicating patients’ ability to effectively manage their symptoms. If successfully adapted for human application, the chronogenetic methodology could treat rheumatoid arthritis at the most advantageous circadian juncture. Guilak and his team have secured funding from the Advanced Research Projects Agency for Health (ARPA-H) to further develop this approach for clinical testing in human participants. Guilak has filed a patent application for the technique created during this investigation. He is also an employee and stakeholder in Cytex Therapeutics Inc., which is advancing the cartilage-based constructs utilized in this research for therapeutic purposes.

The article Study uses body’s clock to deliver medication precisely when needed was first published on The Source.