New drug resets the body clock and cuts jet lag recovery nearly in half

Scientists have identified a compound, Mic-628, that appears to directly influence the body’s internal clock. A research team from several Japanese institutions—including Kanazawa University, Osaka University, Toyohashi University of Technology, and the Institute of Science Tokyo—conducted the research. Their work centers on understanding and potentially manipulating the biological rhythms that govern many bodily functions.

How Mic-628 Works

The researchers discovered that Mic-628 activates Per1, a key gene responsible for regulating daily biological rhythms in mammals. This activation occurs through a specific interaction with a protein called CRY1, which typically suppresses clock gene activity. When Mic-628 attaches to CRY1, it helps form a larger molecular complex—CLOCK-BMAL1-CRY1-Mic-628—that then “switches on” Per1 at a site known as a “dual E-box.”

This process isn’t limited to the brain’s master clock, located in the suprachiasmatic nucleus (SCN). Mic-628 also appears to shift the timing of clocks in other organs, such as the lungs. Importantly, these shifts occurred simultaneously and were not dependent on when the compound was administered.

Did You Know? The research team included Emeritus Professor Tei H. From Kanazawa University, Associate Professor Takahata Y. From Osaka University, Professor Numano R. From Toyohashi University of Technology, and Associate Professor Uriu K. From the Institute of Science Tokyo.

Jet Lag Recovery in Animal Models

To assess the potential real-world impact of Mic-628, the team tested it in a mouse model of jet lag. They simulated a six-hour light-dark cycle shift—equivalent to traveling across several time zones—and found that mice receiving a single oral dose of Mic-628 adjusted to the new schedule in four days, compared to seven days for the control group. Mathematical analysis suggests this accelerated adjustment is driven by a feedback loop involving the PER1 protein.

Why Shifting the Clock Matters

Adjusting to earlier schedules, like those experienced during eastward travel or with night shift work, is often more difficult for the body than adjusting to later schedules. Existing methods, such as light exposure and melatonin, require precise timing and can be inconsistent. Mic-628 offers a different approach because it consistently advances the body clock, regardless of when it’s given.

Expert Insight: The consistent effect of Mic-628, independent of timing, represents a potentially significant departure from current strategies for managing circadian disruption. This suggests a more predictable and reliable method for resetting the body clock, which could have broad implications for individuals struggling with jet lag or shift work.

Future Research

The researchers intend to conduct further studies to evaluate the safety and effectiveness of Mic-628 in both animals and humans. If these studies are successful, Mic-628 could become a valuable tool for addressing jet lag, sleep disorders related to shift work, and other conditions caused by circadian misalignment.

The findings were published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS).

Frequently Asked Questions

How does Mic-628 affect the body clock?

Mic-628 activates Per1, a core gene that regulates daily biological rhythms, by interacting with the CRY1 protein and forming a complex that switches on Per1 at a specific DNA site.

Did the research involve human subjects?

No, the initial research was conducted using a mouse model designed to mimic jet lag.

What makes Mic-628 different from existing methods for adjusting to new time zones?

Unlike light exposure or melatonin, Mic-628 consistently advances the body clock regardless of when it is administered.

Could a drug that reliably resets the body clock improve the health and well-being of millions who struggle with sleep and circadian rhythm disorders?