Baylor Chemist Pursues Novel Drug to Prevent Brain Injury in Newborns
Daniel Romo, Ph.D., provides synthetic chemistry expertise on international team’s $1 million NIH grant to develop treatment for hypoxic-ischemic brain injury
By Derek Smith, Baylor University Marketing & Communications
WACO, Texas (July 27, 2023) – Daniel Romo, Ph.D., The Schotts Professor of Chemistry at Baylor University 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 hypoxic-ischemic brain injury (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, derived from a soft coral found only in Hawaii.
“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—caused by oxygen deprivation to an infant’s brain—which occurs in approximately two out of every 1,000 U.S. births and can lead to permanent neurological damage. One treatment currently consists 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. Romo joined the team to examine the structure and activity relationships of the molecule and to derivatize particular positions of the molecule to ideally improve the properties needed for a drug candidate.
“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.”
In practice, synthetic chemists like Romo and his laboratory team are at the very early stage of drug discovery, and work through many dead ends en route to drug leads. Romo quoted that only one in every 10,000 compounds synthesized actually lead to a drug. However, waixenicin A offers numerous encouraging signs through the team’s research, which took place over more than eight years before earning the NIH grant.
“What gives me optimism is that our starting point is a natural product. Historically, natural products have been a great source of drugs. If you look at most clinically used drugs, about 40-50% come from natural products, and that number increases to about 70% for anti-cancer drugs,” Romo said. “We’re not starting from scratch, but from an information-rich molecule.”
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. David Horgen, Ph.D., a natural products chemist at Hawaii Pacific University, is the project coordinator. Others on the team include Hong-Shuo Sun, Ph.D., Zhong-Ping Feng, Ph.D., and Steven Miller, M.D., Ph.D., of the University of Toronto; and Andrea Fleig, Ph.D., of The Queen’s Medical Center and University of Hawaii Cancer Center.
“It’s incredible to be a part of a team with experts in so many different areas,” Romo said. “It speaks volumes that they’re involved in this project, and we have fun together as we do this work. We’re also blessed to have so many people from our team here at Baylor as a part of the project as well.”
Joining Romo from Baylor is Kenneth Hull, Ph.D., associate research professor and assistant director of the Baylor Synthesis and Drug-Lead Discovery Lab, graduate students Sigrid Kiledal and Mathew Parris, and undergraduate Xi “Becky” Gong. They were recently joined by two postdoctoral researchers Shaik Gouse, Ph.D., and Umamaheswara Rao Boddu, Ph.D., whose hiring was made possible by this new NIH grant.
The team will work to meet numerous benchmarks along the way which could lead to further funding, with the hope of a HIBI drug several years in the future.
“It’s fantastic to me, and sometimes mind-boggling, that God had the foresight to provide an environment where organisms like soft coral can evolve natural products to deal with the diseases that we would eventually encounter,” Romo said. “As synthetic chemists we get to investigate these natural products at the molecular level and harvest their rich-information content to help others.”
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