Dysfunction of the body's internal clock is associated with sleep and anxiety disorders. But in a new study, researchers say they may have found a way to control the internal clock by targeting a protein that regulates it, opening the door to new treatments for such disorders.
The research team, including Thomas Burris, PhD, chair of pharmacological and physiological science at St. Louis University in Missouri, publish their findings in the journal Nature Communications.
Most mammals have an internal clock, or a circadian biological clock. It drives the circadian rhythm that is crucial for physical, mental and behavioral changes over a 24-hour period. Disruption to the circadian rhythm, however, can be detrimental to health, causing sleep disorders and other problems.
According to Burris and colleagues, past research has shown that a protein called REV-ERB plays an important part in regulating the internal clock of mammals. As such, they decided to test how compounds that target this protein affect circadian rhythm.
In their study, the team tested a synthetic drug-like molecule called SR9011 on mice with dysfunctional circadian rhythms that possessed anxious behavior. This molecule, the researchers say, activates the REV-ERB protein.
SR9011 increased wakefulness and reduced anxiety, reward-seeking behavior in mice
The team found that the drug increased wakefulness in the mice and reduced REM (rapid eye movement) and slow-wave sleep. What is more, SR9011 was also found to reduce anxiety and reward-seeking behavior.
Burris and colleagues say their findings are interesting, noting that drugs that increase wakefulness usually increase anxiety, while those that reduce anxiety tend to reduce wakefulness. But the researchers note that "the pharmacological proﬁle of REV-ERB agonists and their ability to target the clock appear to be distinct from these pathways."
As such, the team says SR9011 may be effective for the treatment of both sleep and anxiety disorders. It is estimated that around 50-70 million adults in the US have some form of sleep disorder. Anxiety disorders are the most common mental illness in the US, affecting around 40 million adults.
In addition, since SR9011 was found to decrease reward-seeking behavior, the researchers believe the drug could also be effective in treating addiction.
"Drug addiction clearly has a circadian component, and mice with mutations in clock genes - such as Per1, Per2, Clock and Npas2 - have altered responsiveness to the reward associated with cocaine, morphine and/or alcohol," the researchers explain. "Thus, it is quite reasonable to expect that a small-molecule regulator of the clock would modulate reward-seeking behavior."
Commenting on their overall findings, the team says:
"With recent chemical biology approaches, it has become possible to target certain components of the clock and begin to investigate whether pharmacological modulation of clock function and the circadian rhythm may offer an approach to treat human disease.
In summary, our data indicate that pharmacological targeting of the clock holds promise for treatment of disorders associated with anxiety and sleep disorders, as well as addiction."
Burris and colleagues point out, however, that further research is warranted to determine the effectiveness of SR9011 in humans.
Earlier this month, Medical News Today reported on a study by researchers from the University of Missouri School of Medicine, which claimed that alcohol disrupts the body's internal clock, causing insomnia.