New drug offers promise of relief for insomnia
Baku, December 16 (AZERTAC). Psychiatrist Gabriella Gobbi was testing a new drug on depression in her laboratory when a curious thing happened. The mice fell asleep.
Not the kind induced by sleeping pills but the deep, restorative slumber of childhood.
Conducted in collaboration with scientists in Italy, the discovery of a novel drug called UCM765 is expected to pave the way for new treatment for sleep disorders, which afflict millions worldwide.
Published in the Journal of Neuroscience, the research on rats and mice found that the drug administered under the skin or directly into the brain had a two distinct effects on sleep.
Rats got to sleep 60 per cent faster than the control group that did not get the drug, and they slept longer, increasing non-REM sleep, also known as "deep sleep" by 45 per cent, described Gobbi, an associate professor of psychiatry in the Faculty of Medicine at McGill University.
"We had no idea what it would do. It was like opening a dark box - a totally unknown world. We found it by serendipity," said Gobbi, who led a team from the Research Institute of the McGill University Health Centre (RI-MUHC) on a multi-experiment, seven-year study of melatonin receptors.
In an interesting aside, the study also involved such intrigues as industrial spying, Gobbi said. "A pharmaceutical company tried to do espionage on our results."
Gobbi said she often treats people with sleep disorders and depression and the research was driven by her feelings of great sympathy for insomniacs.
Chemists in Italy who developed the drug from the hormone melatonin in 2005 had initially aimed at alleviating depression and anxiety.
It was also believed that melatonin could alter the circadian rhythm or body clock.
"But its main effect was on sleep," said Gobbi, whose breakthrough discovery unveiled the inner workings of melatonin on two receptors in the brain called MT1 and MT2.
These are localized in one area of the brain, the reticular thalamic nucleus, which is a "powerhouse of (restorative) sleep," Gobbi said.
"It was tough because we went against conventional wisdom on melatonin. We thought both receptors would promote sleep and it`s not true - the receptors have opposite roles."
The team tested the drug on the sleep-wake cycle of rats and mice lacking MT1 or MT2 receptors.
Gobbi`s team induced bursts of activity with the drug in MT2 neurons, a key component of deep sleep.
"It was amazing. When I saw that it was a big emotional moment with my students. Wow. Something new. Someone shouted `Eureka`," Gobbi said.
They found that selectively treating one receptor can have therapeutic advantages without the side effects of sleep medication and antidepressants now marketed for insomnia - for example, drug dependence and cognitive impairment, Gobbi said.
That`s because UCM765, which is not yet in clinical trials in humans, does not destroy the "architecture of sleep," Gobbi explained. Sleep stages remain the same while increasing the time of deep sleep, she added.
About 25 per cent of Canadians have a significant sleep problem that impairs their function during the day and their quality of life, while an estimated 10 per cent are affected by chronic insomnia.
Gobbi`s finding may have significant impact in the future treatment of insomnia, or as a sleep-aid for other sleep problems, said Richard Horner, Canada research chair in sleep and respiratory neurobiology, who did not participate in the study.
"Moreover, that this (drug) analog can target a specific melatonin receptor subtype is the likely key to more focused beneficial effects on sleep than using melatonin itself," he said.
Completely original work and very promising, added Jacques Montplaisir of the Centre d`étude du sommeil at Sacré Coeur Hospital affiliated with Université de Montréal.
"It acts differently than all other molecules we use now," Montplaisir said.
Gobbi`s work is funded by grants from the Fonds de la recherche en Santé du Québec (FRSQ), by the Canadian Institutes of Health Research (CIHR), by the Canadian Foundation for Innovation (CFI), MSBi Valorisation, the McGill University Health Centre (MUHC), and the Quebec Department of Economic Development, Innovation and Exportation (MDEIE).
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