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Nasal Delivery Of Weight-Loss Hormone

ENT

Experimenting with mice, Johns Hopkins Medicine researchers have added to evidence that a hormone best known for helping regulate hunger and body weight might also ease breathing problems experienced during sleep more effectively when given through the nose.

Although clinical trials using the hormone, known as leptin, are not yet on the horizon, the investigators say their success delivering it through the test animals' noses may help them develop easier-to-use therapies for people with sleep-related breathing problems such as sleep apnea.

The findings were published online Oct. 12 in the  American Journal of Respiratory and Critical Care MedicineLeptin, a hormone made by fat cells that were first identified in 1994, targets the brain's appetite center, helping to regulate appetite.

Leptin's potential for treating obesity

"Although leptin's potential for treating obesity and curbing overeating failed to materialize in human trials, its role in the respiratory system has triggered new rounds of therapeutic possibilities," says Vsevolod Polotsky, MD, professor of pulmonary and critical care medicine at the Johns Hopkins University School of Medicine, and senior author of the study. His laboratory has been studying the hormone for more than 20 years.

"A particular focus of his research is the search for new strategies to treat obstructive sleep apnea, a serious and even potentially lethal condition that affects approximately 30% of US adults," Polotsky said.

The prevalence increases to 50% among obese populations. The disorder is marked by frequent, brief periods when breathing stops during sleep due to upper airways closing. The result is oxygen deprivation.

People with obesity are also at higher than usual risk of other sleep-breathing problems called obesity hypoventilation syndrome, in which brain centers that regulate breathing during sleep operate abnormally and fail to increase breathing appropriately in response to carbon dioxide, which results in the buildup of carbon dioxide in the blood. The syndrome often accompanies sleep apnea.

Currently, the most common effective treatment for these sleep problems is CPAP, which mechanically increases air pressure in the throat to keep airways open during sleep.

But because CPAP machines must be worn at all times during sleep and some patients find them cumbersome, uncomfortable, noisy and confining, substantial numbers of people cannot tolerate them and stop their use.

Polotsky says previous research has shown that leptin is essential in regulating breathing, and can successfully treat sleep-disordered breathing symptoms in obese mice lacking leptin. However, mice with diet-induced obesity are resistant to the leptin hormone and failed to respond when leptin was injected into the belly (or abdomen).