Mizzou researchers identify first-ever neurotherapeutic to address muscle weakness

COLUMBIA, Mo. -- While a gradual loss in muscle strength is a natural part of aging, for many older adults it’s more than just feeling a little weaker. Sarcopenia — a condition affecting nearly half of adults over 80 — involves a sharp decline in muscle size and strength, increasing the risk of falls and fractures, impacting overall health, life expectancy and quality of life.

Now, researchers at the University of Missouri have identified a game-changing solution. Their recent study suggests that a small molecule drug that targets a specific serotonin receptor could become the first neurotherapeutic treatment for sarcopenia — offering hope for older adults struggling to stay strong.

“What many people don’t realize is that grip strength is actually a better predictor of health outcomes and even lifespan than factors such as blood pressure,” said W. David Arnold, executive director of the University of Missouri System’s NextGen Precision Health initiative and a professor in the School of Medicine. “This was the first time we have ever shown that a drug can successfully help motor neurons, the final cell that communicates between the nervous system and muscle, to fire more effectively, signal muscle contraction and improve muscle strength. So, this is an exciting breakthrough in our mission to help older adults with sarcopenia.”

The small molecule drug used in the study — which can make motor neurons fire more consistently and reliably — could potentially be used in human clinical trials. And with Mizzou’s Roy Blunt NextGen Precision Health building, which houses both research and clinical spaces, the path to bringing this treatment to patients could be accelerated.

Arnold added that while all adults lose motor neurons as they age, he and his research team are learning that the muscle weakness linked with sarcopenia is less about the loss of the number of motor neurons and more about the steep decline in the ability of motor neurons to repetitively fire to activate muscle movement.

“In this study we were able to show that this small molecule drug can activate motor neurons to make them more able to fire repetitively, which was a huge breakthrough,” Arnold said.

The discovery can also help the research team at Mizzou generate other molecular candidates to achieve the same effect.

“If we can make neurotherapeutics become widely available, it can improve the quality of life for so many older adults by improving their strength and balance, helping them stay mobile and independent as they age,” Arnold said.

“5-HT2C agonism as a neurotherapeutic for sarcopenia: Preclinical proof of concept” was published in GeroScience. Mizzou’s Nathan Kerr, a postdoctoral researcher in Arnold’s lab, was the lead author on the study, which was funded by the National Institute on Aging.