Pioneering Research to Fight Brain Disease in Newborns

Approximately two out of every 1,000 births in the United States can lead to permanent neurological damage due to hypoxic-ischemic brain injury (HIBI) in newborns.

Daniel Romo, Ph.D., The Schotts Professor of Chemistry and co-director of the Baylor Synthesis and Drug-Lead Discovery Lab, is providing synthetic chemistry leadership on an international team of researchers in pursuit of a groundbreaking drug to treat HIBI in newborns. The National Institutes of Health (NIH) has awarded the team a grant of more than $1 million to pursue further research and development of the drug.

“This is truly a collaborative grant, and we are happy that the NIH decided to move this forward,” Romo said. “We believe this has a lot of potential to treat HIBI, and it has implications for stroke as well. We are glad to be part of an incredible team of scientists, each bringing their own unique skills and expertise, to conduct research that will have a beneficial effect for infants.”

No drugs exist to treat HIBI with only one treatment currently consisting of whole-body cooling to slow an infant’s metabolic processes.

“Although rare, there are a number of reasons that HIBI can affect the most vulnerable during labor or birth,” Romo said. “A lack of oxygen to the brain may lead to the death of neuronal cells, which can ultimately result in brain injury. This can of course lead to serious issues that affect the rest of a person’s life.”

Romo’s expertise is in the synthesis of naturally occurring small molecules that can yield early drug leads, and his renowned research has led to new synthesis strategies that address diseases like cancer, Alzheimer’s and more. A soft coral found only in Hawaii is the focus of the team’s research, and their work is centered on a unique natural molecule, called waixenicin A.

Waixenicin A displays properties that block a key point in a cascade of events that can lead to HIBI.

“The main overall idea is to prevent neuronal cell death. Our collaborative team found that waixenicin A inhibits an ion channel that is critical during the early stages of neuronal injury,” Romo said. “When hypoxia occurs in an infant, there’s a cascade of cellular events that impacts the brain. One of those events involves an influx of calcium into neuronal cells mediated by this ion channel — TRPM7 — which is responsible for a large calcium influx into cells. Amazingly, this soft coral-derived molecule shuts this ion channel down, preventing calcium influx thus preventing neuronal cell death.”

Romo is one of five co-principal investigators on the grant, which funds research for the next two years, with the possibility of an additional three years of funding if milestones are met.

“It’s incredible to be a part of a team with experts in so many different areas,” Romo said.