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The promise of 'chronotherapies' — treatments timed for just the right biological moment

The promise of 'chronotherapies'
“The ticking of the bodyclock can help us fight cancer, safeguard our hearts, time our meals, and enhance our intelligence.”

The study of chronobiology and its effects on health and disease — a field of research that has deep roots here in Minnesota — has taken off in recent decades, although its ramifications have yet to reach the broader public consciousness.

Most people think of chronobiology (if they think of it at all) in terms of their sleep cycle — whether they are a “morning” or an “evening” person, for example. And a few might connect it to the negative effects of jetlag and shift work.

But, as a recent long article in the digital magazine Aeon points out, acknowledging and understanding chronobiology — the innate biological rhythms that control all of our biological functions — has much broader ramifications.

“The ticking of the bodyclock,” the article declares, “can help us fight cancer, safeguard our hearts, time our meals, and enhance our intelligence.” 

Timing medical treatments

The author of the article, science journalist Jessa Gamble (“The Siesta and the Midnight Sun: How our Bodies Experience Time”) describes many aspects of chronobiology research. But what I found most interesting was her discussion of chronotherapy. This is an approach to medicine that uses daily (circadian) biological cycles to time various drug and other therapies “for just the moment when our pathogens are most vulnerable.” 

As Gamble notes, some of the most impressive work in chronotherapy comes from the field of cancer treatment, “where it has been noticed for more than 30 years that chemotherapy is more effective — and less arduous — when delivered at certain times of day. That’s because tumours grow on a rhythmic schedule, and that schedule does not match the growth timetable of healthy tissues that might fall victim to whole-body anti-cancer drugs. Organs that oncologists normally try to isolate in space can also be separated by time differences.”

“For some anti-cancer drugs, the optimal time to deliver treatment could be in the middle of the night,” one oncologist tells Gamble. “Chronotherapy can improve some adverse events up to five-fold as compared to constant rate infusion, and as compared to wrongly timed delivery.” 

Applications for heart disease

But cancer isn’t the only disease that chronobiologists are tackling with timed therapies. Chronotherapeutic approaches to treating heart disease — chronocardiology — is also being actively explored. Writes Gamble:

[A] heart attack is more likely on a Monday than on any other day of the week. It’s our behaviour that makes the day of the week a biological reality — staying up later at the weekend leads to a jarring disruption on Monday, when the workday reasserts itself again.

The morning, in particular, carries danger for a cardiac event. Tami Martino runs a chronocardiology lab at the University of Guelph in Canada and studies the runaway blood-clotting process triggered by cardiovascular disease. The platelets that form those clots tend to build up between 8am and 9am. When one of those clots blocks an artery, that’s when we see heart attacks and strokes and, indeed, mid-morning is the danger zone for cardiac events.

According to Martino, the cardiomyocyte circadian clocks in the heart’s muscle tissues — the ones that make the heart beat — also dictate the damage incurred by a heart attack. When cardiac arrest is induced in mice in the early evening, which is when they first wake up, that cardiac event takes more than three times the toll of a heart attack in the early morning as they are falling asleep.

Knock out the cardiomyocyte clock genes that keep track of the time of day, and heart attacks at any time of day have the same minimal damage. The chronomedicine approach to cardiology would include making sure blood-pressure medication or blood thinners are in circulation during the most vulnerable period above all others. Knowing that circadian clock time can mean the difference between life and death is a major strategic advantage against the most common cause of death in the Western world.

Still ‘on the horizon’

“Imagine a future in which every prescription carries a time stamp, and even an over-the-counter remedy such as Paracetamol (Tylenol), profoundly rhythmic in its liver toxicity, sports a label with timing instructions,” writes Gamble. “Next to your blood type, your medical records could include your chronotype, which your work hours also reflect.” 

That’s certainly imaginable, but what’s less clear is just when this promised vision might become a reality. I recall being similarly enthusiastic about chronotherapy’s potential in a book I co-authored on the topic more than 25 years ago.

We haven’t made as much progress as the experts I spoke with then had hoped, but, of course, that doesn’t mean breakthroughs in this field aren’t being made.

They are. But, as with so much medical research, translating those breakthroughs into universally accepted and practical clinical applications has turned out to be much more complicated than originally believed.

Time will tell.

FMI: You can read Gamble’s article in full on Aeon’s website. 

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