Growth factors could be key to warding off symptoms of amyotrophic lateral sclerosis and aging

Gregorio Valdez in the laboratory

Jim Stroup/Virginia Tech

Gregorio Valdez, PhD

An early-career researcher at the Virginia Tech Carilion Research Institute has won his first major independent grant from the National Institutes of Health. And if his research pans out, the result could be a therapeutic technique to slow – or even stop – the onset of the most debilitating symptoms of amyotrophic lateral sclerosis, better known as ALS.

Gregorio Valdez, an assistant professor at the Virginia Tech Carilion Research Institute, will spend the next three years looking to see whether a specific subset of growth factors may hold therapeutic potential for slowing or even stopping ALS. Known as fibroblast growth factors 7, 10, and 22, these three proteins are heavily involved in the formation of synapses during development. And if Valdez’s hunch is right, the growth factors may also be able to protect and repair neuromuscular junctions, the synaptic connections between nerves and muscles.

The grant allowing Valdez to test this hypothesis will seed $678,000 over a three-year period to his laboratory. Dubbed a K01 award from the National Institutes of Health, the grant is designated for tenure-track researchers less than three years removed from their postdoctoral positions to help flesh out their ideas and become more competitive for larger awards.

“We think that if we can protect the neuromuscular junctions from the destructive mutations that typically lead to ALS, then perhaps we can slow down or even stop the disease’s degradation of motor skills,” said Valdez. “But the research doesn’t stop at ALS. What we learn could be applicable to repairing and maintaining synapses throughout the central nervous system. We may be able to stop the degradation that occurs as a part of normal aging as well.”

The efforts of Valdez’s research during the coming years will primarily involve mice. Researchers will first remove fibroblast growth factors from a mouse model for ALS that recapitulates all the symptoms seen in humans with the same mutation.

But these initial experiments only speak to the necessity of the growth factors to normal health, Valdez said. To see whether they could be used as therapeutics, his laboratory will induce the overproduction of these growth factors.

“This is the most critical part of the experiment – to crank up the signaling mechanism of the growth factors,” said Valdez. “This will show whether we can truly slow the disease.”

The final prong of the research will investigate whether there might be an issue with the “bridge” between the cells’ synapses that is stopping the growth factors from crossing. Both aging and ALS can cause changes in the structures between the two terminals of a synapse, which can stop important molecules and proteins from passing between cells. If this proves to be true in ALS, researchers would aim to generate biologics to fix the bridge so that the growth hormones can function properly.

“We expected great things from Dr. Valdez when we hired him, and I believe this grant is only the beginning for his growing laboratory,” said Michael Friedlander, executive director of the Virginia Tech Carilion Research Institute. “Besides being important to Dr. Valdez’s early career, this research holds great promise not just for ALS patients, but also for an aging population that will face many challenges in the decades ahead.”

Written by Ken Kingery