$1.9M NIH Grant Supports Study of Ways to Preserve Swallowing, Breathing

The National Institutes of Health (NIH) has awarded a $1.9 million grant to University of Missouri (MU) researchers to study ways of preserving essential functions like swallowing and breathing in people with amyotrophic lateral sclerosis (ALS) and other motor neuron diseases.

This four-year grant was awarded to co-principal investigators Nicole Nichols, PhD, of the MU Dalton Cardiovascular Research Center and an assistant professor at the MU College of Veterinary Medicine, and Teresa Lever, PhD, a professor of otolaryngology at the MU School of Medicine.

In motor neuron diseases, motor neurons — specialized nerve cells that control voluntary movement — degenerate and die, leading to difficulties in swallowing, speaking, and breathing, in addition to walking problems.

“But not all [motor neurons] die at the same time, and some will continue to live,” Lever said in a university news story.

“If we intervene at an earlier stage in the disease process, are we altering the fate of the dying cells or are they still dying? And are we affecting surviving cells so they can pick up the slack of dying cells? That’s what we want to find out,” she added.

Lever and Nichols aim to understand how swallowing and breathing deteriorate in people with ALS and diseases like spinal muscular atrophy. They also will assess whether tailored tongue exercise may help preserve these functions.

“Many people think the tongue is just important for speaking and swallowing, but it’s also critical to breathing,” Lever said.

“If it’s not doing its job, the upper airway can collapse. And we see that in a lot of neurological conditions,” she added. “If we can preserve tongue function for swallowing, it should also promote breathing.”

Researchers will use a non-invasive and individualized tongue strengthening program to evaluate whether it aids swallowing and breathing in a rat model of tongue dysfunction that mimics some aspects of ALS.

Previously developed by a research team that included Lever and Nichols, this model involves selectively eliminating the animals’ motor neurons responsible for upper airway function.

Researchers will first measure each rat’s lick force while drinking water from a spout, using a device called a “force lickometer.” Then, twice a week, the rat’s standard water bottle will be switched to one using a specialized spout that can be adjusted to require greater tongue strength to access the water.

According to the release, the rats will voluntarily drink water “hundreds of times” over the 12 nighttime hours they are most active. The adjusted spouts serve as a low-resistance  and high-repetition training program similar to those used for building body strength and endurance.

Study results will help determine the mechanisms through which exercise helps to preserve upper airway function in the surviving motor neurons responsible for swallowing and breathing, and for coordination. This may support future studies in people with motor neuron diseases.

The project will involve other MU researchers in various disciplines, including Lixin Ma, PhD, a professor of radiology at the MU School of Medicine; Filiz Ersoy, PhD, an assistant research professor in the Department of Electrical Engineering and Computer Science at the MU College of Engineering; and Mojgan Golzy, PhD, an assistant research professor in Health Management and Informatics at the MU School of Medicine.

“This really is a multidisciplinary effort across the University of Missouri,” said Nichols, “to advance a field where there is still so much that is unknown.”