Sleep Research in the Blind May Help Us All

Greater control of the circadian system can help us understand the extent to which it maintains our overall health and well being, and help to regulate complex metabolic systems that, if disrupted, can increase the risk of disease.
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We live in an increasingly 24/7 society, with work, family, and social pressures all chipping away at our sleep. Couple this with long work hours, shift-work, chronic caffeine use and exposure to the glow of computer screens late into the night, and it may be much more than sleep that suffers. We may also be throwing off the body clock, or circadian rhythm, and its control of hundreds of body processes that keep us healthy and feeling well. While much is yet to be learned, there is growing evidence that a misaligned body clock can contribute not only to sleep problems, but also increase risk of developing diabetes, depression, obesity and even some forms of cancer.

For the past 60 years, neuroscientists have been studying the role of light in regulating the body's circadian rhythm. Since the early days of studying sleep in caves and underground laboratories, we've been able to determine that light exposure is the great circadian regulator. Most of us naturally have a body rhythm a little longer than 24 hours -- and light is the major environmental time cue that resets the clock in our brains each day so that we remain synchronized with the 24-hour day. In turn, the clock regulates our sleep and wake cycle, our mood, alertness and performance patterns, hormones, heart rate, and many other functions.

What happens to your sleep and circadian rhythms if you can't see light? To answer this question, my colleagues and I at Brigham and Women's Hospital in Boston have studied sleep and circadian rhythms in totally-blind patients for more than 20 years. A majority of this population suffers from a little-known but highly disruptive condition called Non-24-Hour Sleep-Wake Disorder that robs them of the ability to keep "in sync" with society's 24-hour schedule. Current research to develop a substitute time cue to reset the body clock in this group, if successful, would not only change their lives, but also help understand the mysteries of circadian rhythms and how they impact all of our lives.

Without the daily reset that light provides, the body clock essentially runs on its own internal clock time, usually putting the person to sleep later and later each day. Eventually, sleep is pushed into the daytime, causing overwhelming daytime sleepiness and chronic insomnia at night for sometimes months at a time, before being pushed all the way around the clock, and starting all over again.

Sufferers with Non-24, which is estimated to afflict up to 95,000 totally-blind people in the U.S., say it's like having never-ending jet lag. They are often so sleepy that they fall asleep in mid-sentence or simply can't get out of bed. They find it extremely difficult to be on time and stay awake at work, attend school, pursue interests or just plan dinner or drinks with family and friends.

Help is on the horizon, however. My institution is involved in one of the largest clinical programs ever undertaken to determine if an intervention other than light can safely and predictably regulate the body clock in totally-blind people with Non-24. Previously, in much smaller studies, we and others had shown that daily treatment with a synthetic version of the hormone melatonin could reset the circadian clock. Sold as a dietary supplement, melatonin comes in many strengths, preparations and levels of purity and has not undergone the rigorous safety tests that are required for FDA-approved medications. Determining when to take it, or the best dose and preparation to use, was tricky and is still not clear. There is an effort underway, however, to test a drug for Non-24 that works like melatonin. These studies are designed to determine whether this treatment is effective, how and when it should be taken, and whether or not it is safe, based on FDA guidelines. My lab is involved in these studies, which are still underway at the moment.

The promise of an approved drug intervention that can reset the clock of patients with Non-24 would mean that those affected would be able to live on a normal day-night cycle, with all the health and social benefits that would entail. We would also have important new information that can help further our understanding of the broader role of the circadian clock, or the consequences of a mistimed clock. We can look at ways to address other serious circadian rhythm disorders, including shift work, frequent travel across time zones, and delayed sleep phase syndrome. This research may also contribute to the emerging field of chronomedicine -- understanding when is the best time to take medicines for best results.

Greater control of the circadian system can help us understand the extent to which it maintains our overall health and well being, and help to regulate complex metabolic systems that, if disrupted, can increase the risk of disease. Circadian alignment may even one day be evaluated routinely as an important indicator of overall health. In medicine, as in much of life, timing is everything.

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