FDA-approved drug may help restore breathing in obesity-related sleep disorder

Researchers from the George Washington University have uncovered promising evidence in an animal study that shows setmelanotide, an FDA-approved medication for a rare genetic obesity disorder, may offer a pathway for treating a life-threatening form of sleep-disordered breathing called Obesity Hypoventilation Syndrome.

People with this syndrome don't breathe deeply or frequently enough, especially during sleep, which leads to a buildup of carbon dioxide in their bodies even when they're awake. 

Obesity Hypoventilation Syndrome which affects an estimated five to 10 million Americans commonly coexists with obstructive sleep apnea. While positive airway pressure machines like CPAP and BiPAP are standard treatments used to help keep airways open while sleeping they provide limited help to people with Obesity Hypoventilation Syndrome.

Our research addresses a critical gap in treatment options for Obesity Hypoventilation Syndrome. Our findings could be the first step toward a much-needed treatment for a life-threatening condition that impacts millions."

Vsevolod Polotsky, professor of anesthesiology and critical care medicine at GW's School of Medicine and Health Sciences

Polotsky and postdoctoral researcher Mateus Amorim used the FDA approved drug setmelanotide to see if it could help improve breathing in obese mice. Researchers targeted a protein found on certain neurons in the brain called MC4R pathway that helps the brain control how much mammals and humans eat, how much energy they burn and even how they breathe. 

Key Findings: 

• Just one dose of setmelanotide improved breathing and helped the mice respond better to high levels of carbon dioxide - something that's often impaired in Obesity Hypoventilation Syndrome.

• Setmelanotide improved breathing more than would be expected just from boosting metabolism, meaning it likely acts directly on brain regions that control breathing.

• When using special tools to turn on MC4R neurons, they found breathing improved. But when those same neurons were turned off, breathing got worse - even when setmelanotide was given. 

• They also discovered that MC4R neurons connect directly to other brain cells that control the diaphragm, the main muscle used for breathing.

This is the first direct evidence that the MC4R pathway plays a critical role in how the brain controls breathing in obesity. Setmelanotide may be able to treat Obesity Hypoventilation Syndrome by bypassing the leptin (a hormone made by fat cells that helps regulate breathing) which is common in people with obesity.

While more studies of setmelanotide for Obesity Hypoventilation Syndrome are still needed, this research represents a major advance in understanding how the brain controls breathing in obesity.

The study, "Targeting melanocortin 4 receptor to treat sleep disordered breathing in mice" was published in The Journal of Clinical Investigation.