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When that good night's sleep becomes elusive, sometimes the only option is medication. But the sleeping pills now on the market often come with risks that may outweigh the benefits, inducing dependency, withdrawal symptoms, and occasionally even cognitive impairments such as short-term amnesia.
Not so with Circadin, a new drug produced by Neurim Pharmaceuticals and based on the research of company founder and chief scientific officer Prof. Nava Zisapel at Tel Aviv University.
Unlike other sleep medications which suppress brain activity, Neurim says that Circadin works with the body's natural processes to induce a restful, restorative sleep. It does so by gradually releasing melatonin in the body - the hormone that prepares the body for sleep.
Possibly the worst aspect of insomnia is its deleterious effect on daytime functioning. That's where Circadin has an additional edge over its competitors.
"Circadin not only improves the onset of sleep but also the quality of sleep," Zisapel, a neuroscientist, told Israel21c. "People who take the drug have reported that they have better daytime functioning and an improved quality of life."
The drug is already being distributed here and in some European countries by Neurim, which was set up in 1991 by Zisapel and her husband Yehuda Zisapel (founder of the RAD Group), to develop treatments for age-related disorders. It is now in the process of obtaining approval from the US Food and Drug Administration.
Melatonin is produced in the body at the onset of darkness, preparing the body physiologically by lowering the blood pressure and body temperature. Its primary function is to separate day and night in the body's internal biological clock.
Since darkness is a trigger of melatonin, strong fluorescent lights can suppress its production. But other factors may also be involved: Anxiety, depression, or simply aging can suppress the production of melatonin and cause insomnia.
"People may start sleeping less well when they age," Zisapel points out. "The brain structure changes with age, and may lose the ability to produce melatonin if the pineal gland becomes calcified. It doesn't happen to everyone at the same age, but in general, people who begin to get gray hair are losing the ability to produce melatonin."
Circadin is therefore a hormone replacement therapy that becomes applicable if the pineal gland - the gland which produces melatonin - stops doing its job sufficiently.
Releasing melatonin gradually Zisapel describes how Circadin works in a way that mimics the activity of the pineal gland. "Circadin produces melatonin in the same way as the gland: It starts slowly at around 10 p.m., gets to a peak at around 2 a.m., and gradually stops by the morning. It releases melatonin in a gradual manner."
In reaching this point, it's been a long road for Zisapel, who began developing the formula in 1992 in her neurobiology lab at Tel Aviv University. Because Circadin was a new kind of sleep medication, regulators insisted on much more clinical data than they had with other medications. The drug was finally approved for the market in Europe in 2007.
Zisapel became interested in the effects of melatonin during her post-doctoral work at the Weizmann Institute of Science in Rehovot and researched the hormone's effect on animals for a decade before beginning to apply that research to humans. Now she is also researching a treatment for Parkinson's disease, as well as a treatment for insomnia that is induced by pain and depression.
Circadin recently completed a clinical trial in the US, which tested the drug for its efficacy in patients between the ages of 18 and 55. Until then, the target population for the drug were patients over 55, but the Food and Drug Administration required that Neurim, which performs R&D in Tel Aviv and business development in Switzerland, expand its research to include younger patients.
"We just finished one study that shows what's going on in whole population over 18 and the drug is still effective, but we feel that patients aged 55 and older benefit the most," says Zisapel. (Israel21C)