November 30, 2017

Team to research radiation exposure drugs

Two-year Department of Defense contract could provide $8M in funding



The U.S. Department of Defense, through the U.S. Strategic Command, has contracted with the University of Nebraska National Strategic Research Institute to help establish a drug development pipeline that could speed the process of developing new drugs at the Armed Forces Radiobiology Research Institute to counteract the effects of radiation exposure.

The National Strategic Research Institute is one of only 13 University Affiliated Research Centers in the country, and the only one with a primary mission responsibility to deliver research solutions for combating weapons of mass destruction (chemical, biological, radiological and nuclear).

David Berkowitz
David Berkowitz

This two-year contract will be conducted through a collaborative effort involving the University of Nebraska-Lincoln’s David Berkowitz, the University of Nebraska Medical Center’s Ken Bayles, and other University of Nebraska System researchers and partners with major pharmaceutical companies across the United States.

The first year of funding, $812,000, will be used to conduct primary analysis of potential dual-use drugs that could be used to counteract radiation exposure. The findings from this initial phase of research could expand into additional options for research with potential additional levels of funding approximating $7.1 million.

“This makes a strong statement about the quality of work being done at the University of Nebraska,” said Bayles, associate vice chancellor for basic science research at UNMC and a co-investigator on the project. “The U.S. government is looking for help with finding drug solutions to treat the effects of radiation exposure, collectively known as acute radiation syndrome, or ARS. They are investing in our university to speed the process for developing these drugs.”

Berkowitz, Willa Cather Professor of Chemistry and director of Interdisciplinary Therapeutics Research at Nebraska, noted that the project “provides an excellent platform for inter-university collaboration – from the fundamentals to translation.

“The potential opportunities that could result from this contract are exciting,” he said. “We’re hopeful that it could lead to a better understanding of ARS and new approaches to both preventative and therapeutic agents for this syndrome and related conditions.”

The project lays out four base tasks in the first year. The first task is to develop a concept refinement study for drug discovery and development.

“The research in pharmaceutical companies is most focused on developing new drugs that people will take over the course of their lifetime,” Berkowitz said. “They don’t have the resources to devote to finding therapeutics for ARS, which can take years to develop and are much less profitable.”

There are numerous drug candidates that languish in the early stages, often under the auspices of a start-up company, where resources are limited to develop the lead compound before the new product brings in revenue from real customers.

That’s where the University of Nebraska comes in. Berkowitz said the University of Nebraska–Lincoln’s Department of Chemistry has an outstanding record of both translational research and of training scientists in organic chemistry, metabolomics and enzyme inhibitor development, areas closely related to what goes on in top pharmaceutical companies.

As a result, Husker chemistry alumni are well represented in pharma, and the institution is a natural partner for pharma, a potential long-term benefit of this project.

“We will need to look for ways we can counteract the medical ramifications of broad radiation exposure,” Bayles said, citing anti-inflammatory drugs, antibiotics, stem cell therapies, and bone marrow growth stimulators as possible solutions. “Ideally, we’d love to discover dual-purpose drugs that could not only be used to treat radiation exposure but also could be used in another capacity, such as for cancer patients undergoing radiation treatment.”

Berkowitz cited the opportunity “to truly build a bridge between the Lincoln and Omaha universities — from basic synthetic, medicinal and analytical chemistry to drug formulation, delivery, pharmacokinetics and animal model studies.

“If this project can build out such a collaborative structure,” he said, “the whole will be much greater than the sum of its parts across the NU/I-80 corridor.”

Bayles said the project will eventually form a large multi-institution collaboration focused on various aspects of treatment for ARS. He also cited Babu Guda, UNMC’s chief bioinformatics/research computing officer, Robert Powers, professor of chemistry at Nebraska, and Tomas Helikar, assistant professor of biochemistry at Nebraska, as key participants in this study.

“This project is a perfect example of how the NSRI leverages the expertise and collaboration potential across the University of Nebraska to truly make a difference in supporting our warfighters, first responders, and possibly the health of Americans citizens,” said Robert Hinson, founding executive director of the University of Nebraska’s National Strategic Research Institute and a retired lieutenant general in the U.S. Air Force. “This should be a great source of pride for Nebraska and the university in leading the way on this very important endeavor.”