March 30, 2020 | Growing appreciation in the research community about the impact of when we sleep, eat, and take our medicines has resulted in more interventional clinical trials aimed at correcting disturbances in the body’s complex of circadian clocks. It’s difficult work with potentially far-reaching implications for everything from losing weight and preventing preterm births to treating diabetes and prolonging survival from devastating cancers.  

In a comprehensive, three-part series on the topic, leading researchers from Harvard Medical School, Washington University, and the University of Geneva share what their respective labs have been learning about the human circadian timing system that is directly relevant to everyday health and treatment outcomes. We begin with an overview of the opportunities and then explore some of the more fascinating discoveries and chronomedicine as the ultimate personalized medicine.   

In part one, we hear about the importance of timing in both diagnostic testing and drug administration from Harvard’s Elizabeth Klerman, M.D., Ph.D., who is also part of the research staff at Massachusetts General Hospital. Klerman is interested in helping narrow the rather sizeable gap that exists—pretty much everywhere—between scientific knowledge and clinical practice. 

In part two of the series, Klerman also discusses her work on time-restricted eating, the association between melatonin and contractions during pregnancy and the potential of light therapy to reduce symptoms in people with Parkinson’s disease and Alzheimer’s. Researchers have been puzzling over the body’s rhythmicity for decades and the governing forces include not only an individual’s feeding patterns and rest-activity cycles but also hormones, nerve impulses, and temperature cycles, as explained by Charna Dibner, Ph.D., a principal investigator in the Diabetes Centre at the University of Geneva. She has been experimenting with a molecule that modulates circadian clocks specific to the pancreas. 

Erik Herzog, a neuroscientist and professor at Washington University as well as president of the Society for Research on Biological Rhythms, weighs in throughout the series. In part three, he talks about the influence of the body’s master clock—which he compares to the atomic clock in Boulder that keeps Apple watches and computers synchronized—on various regions of the brain. He now has a trial underway to test his theory that dosage timing of temozolomide, the standard treatment for glioblastoma, can help extend the life of patients by a precious few months. 

Drug timing studies could one day translate into highly personalized medicine where doctors routinely prescribe medicines according to the sleep schedule of individual patients, Herzog says. But as he goes on to explain, there are a multitude of reasons why this may take years, including the cost and complexity of adding a comparator arm to trials for morning vs. evening dosing. 

As Klerman points out, circadian medicine remains an emerging field, albeit one with a lot of untapped potential based on what is already known about the rhythmicity of living organisms. After reading the series, don’t be surprised if you start checking the clock before grabbing that late-night snack, and you may want to think twice before accepting shift work—or call your doctor about the medicines you’ve been mindlessly taking with your morning coffee. There can be real consequences to working against your body’s programming.   

—Deborah Borfitz, Senior Science Writer, Clinical Research News