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Researcher alert to finding a cure for sleep disorders

J. Ryne Danielson | daniejer@musc.edu | April 14, 2017

Researcher Dr. Meng Liu and his team is working on narcolepsy, sleep disorder research.
Photo by J. Ryne Danielson
Research specialists Bingyu Zou, from left, and Emmaline Bendell join Dr. Meng Liu at his lab bench. Liu is hard at work on a cure for narcolepsy, a sleep disorder that affects more than 200,000 Americans.

Sleep plays an important role in physical and mental health: It boosts the immune system, improves problem-solving and memory retention, supports healthy growth and development and even helps stave off depression. But for those with narcolepsy, a neurological disorder that impairs the body’s ability to regulate sleep, it can be dangerous and life-altering.

Assistant professor Meng Liu, M.D., Ph.D., is one of many researchers in MUSC’s Department of Psychiatry and Behavioral Sciences hard at work on finding a cure for narcolepsy and other sleep disorders. Three new grants from the National Institute on Aging and National Institute of Neurological Disorders and Stroke, both a part of the National Institutes of Health, will help him continue that work at MUSC. The first, a K01 career development grant, will provide Liu with support on the path to becoming an independent investigator in sleep neurobiology. The second, an R21 exploratory grant, will set the foundation for mapping out emotional circuits in the brain that can trigger narcolepsy. And the third, a 5-year R01, will seek to develop a cure for narcolepsy using targeted gene therapy. Altogether, they total more than $2 million.

Dr. Meng Liu and his team focus on narcolepsy, sleep disorder research. 

Dr. Meng Liu has been awarded three new NIH grants, totaling more than $2 million, to develop a cure for narcolepsy.

 

Liu grew up in Hulan Erji, a small town in China’s far north, about 1,000 miles from Beijing. After obtaining both an M.D. and a Ph.D. at Peking University, he came to the United States to pursue molecular biology and gene therapy research — first at Harvard, then at MUSC, when his whole lab relocated in 2011.

Liu’s wife, Bingyu Zou, works alongside him as a research specialist. They have a daughter, Irene. Outside of the lab, art is just as important to them as science. His wife enjoys oil painting. Their daughter plays piano. Liu plays drums and saxophone. He even had a rock band at Harvard.

Since coming to MUSC, he hasn’t had as much time to play. He’s far too preoccupied with his current research and the potential for a cure for narcolepsy.

“Narcolepsy is linked to a missing peptide in the brain,” Liu said. “We think reintroducing it to the brain may cure or treat narcolepsy, but there’s currently no way to deliver it. It disappears quickly in the bloodstream and cannot penetrate the blood-brain barrier.”

That peptide — discovered almost simultaneously in 1998 by two teams that each named their discovery something different — is called, alternately, orexin or hypocretin. It is produced in specific neurons throughout the brain and essentially keeps the brain awake. In people with narcolepsy, those peptide-producing neurons die for reasons that researchers don’t fully understand but may be related to an autoimmune disorder.

To overcome the challenge of delivering the peptide to the brain, Liu is turning to an experimental treatment that has already had success in treating other diseases, from sickle cell to some cancers: gene therapy. By modifying viruses — called vectors — to act as tiny cargo ships, researchers can use them to carry genetic material through the blood-brain barrier. Liu believes he can use this technique to introduce more orexin into the brains of people with narcolepsy in the future.

Just adding orexin alone won’t work though, he said. For one, in the worst cases of narcolepsy, more than 80 percent of the original orexin-producing neurons may have been killed, leaving vectors with no targets. “We can’t put back it into the same spot because the original carrier is gone.”

Instead, a more detailed map of the underlying brain circuitry is required, and Liu believes that might start with a better understanding of the specific triggers of narcolepsy. Strong emotions, for example.

“Surprise, love, fear, laughter — these can cause a sudden loss of muscle control in people with narcolepsy, which is called cataplexy,” Liu explained. “We need to better understand how emotions trigger cataplexy in the emotion regulation center of the brain, the amygdala.”

Once Liu has mapped out the processes in the brain that trigger cataplexy and other symptoms of narcolepsy, he hopes it will be easier to identify specific surrogate neurons to target with new orexin genes.

Once he has that map, Liu will move from animal models to humans, and he will be one step closer to a cure.

“We’re working very hard,” he said, adding that while’s he’s appreciative of his recent grants, grants alone do not always provide adequate support. Liu’s team is entirely grant-funded, and with proposed cuts to the NIH looming before Congress, he’s concerned. “We are anxious. But our psychiatry department is helping us now. If we have support, we’ll do more science, and everyone will have a happier life.”