Oksana Lockridge, Ph.D., professor in the Eppley Cancer Institute, hadn’t meant to study chemical weapons when she began her research into butyrylcholinesterase, some 40 years ago.
When she first started her career-long study of the enzyme, it was because medical experts were concerned that some people reacted abnormally to a certain muscle-relaxant drug when undergoing C-sections, vasectomies and other surgeries which required intubation.
“My goal was to determine why some people reacted abnormally to this drug,” Dr. Lockridge said. “And we solved that problem.”
That was a big deal. But it didn’t take long before she and others realized this discovery might have other applications.
“The importance of her findings were quickly recognized by scientists at several government laboratories, in particular those at the U.S. Army Medical Research Institute of Chemical Defense (USAMRICD) at Aberdeen Proving Ground, Maryland, and at the Walter Reed Army Institute of Research in Washington, D.C.,” said David Lenz, Ph.D.
Dr. Lenz was at the USAMRICD from 1969 to 2011. He directed the project which led to the granting by the Food and Drug Administration of investigational new drug (IND) status to human plasma derived butyrylcholinesterase (BuChE) in 2005.
“Much of the research carried out by Dr. Lockridge on BuChE contributed to the ability of the Army to gain IND approval for this product,” he said.
Today, Dr. Lockridge is working on a project which is part of the university’s partnership with the U. S. Strategic Command (USSTRATCOM) and the National Strategic Research Institute (NSRI). NSRI is a Department of Defense University Affiliated Research Center (UARC) with the University of Nebraska campuses.
The U.S. military hopes to use technology developed by Dr. Lockridge as the next step toward protecting military personnel from nerve agents — chemical weapons.
Dr. Lockridge has developed a method to extract and purify butyrylcholinesterase. Butyrylcholinesterase can act as a pre-emptive vaccine, Dr. Lockridge said, preventing chemical weapons from harming people.
It’s no secret why the military would come to UNMC for butyrylcholinesterase. Dr. Lockridge is recognized throughout the scientific community as one of the world’s leading experts in this subject.
“When you mention Oksana Lockridge, you are talking about a great scientist and the nicest person in the world,” said Chang- Guo Zhan, Ph.D., professor of pharmaceutical sciences at the University of Kentucky College of Pharmacy. “Oksana is truly a pioneer and world-leader in butyrylcholinesterase-related research. Her breakthrough research in the field has established a solid foundation for many other scientists in the world to follow.”
It all started when she and her team found that those who reacted badly to the muscle-relaxant drug during surgeries had a mutation in their butyrylcholinesterase — a protein in the blood of 99.9 percent of the population.
How did they find it? “We were one of the first groups in the country to jump into DNA sequencing,” Dr. Lockridge said.
“That was a long time ago.”
In order to solve the problem, Dr. Lockridge developed a method of purifying butyrylcholinesterase, to fight the drug’s effects. Her method is now used worldwide.
The next step was to find a method to detect exposure — because it turned out this surgery drug had similar chemical properties to (then) commonly used farm pesticides.
“From a low level of exposure, you wouldn’t even have any symptoms,” Dr. Lockridge said. “But I could still detect it.”
This was important to those who handled these pesticides. Some people regularly worked with it in mass quantities. The repeated exposure to large quantities put some people at risk of overexposure.
It was like handling chemical weapons.
“They are chemically similar,” Dr. Lockridge said, “and when they kill you they kill you in the same way. They inhibit your nerve impulse so you can’t breathe.”
Dr. Lockridge is well known for being the first scientist to show that animals can survive without acetylcholinesterase (ACHE), the target of insecticides and nerve agents. Together with other scientists at UNMC, including Angie Rizzino, Ph.D., Dr. Lockridge used transgenic animal technology to show that animals without any ACHE could survive.
“Essentially, Dr. Lockridge’s research changed medical dogma, it was so dramatic that very few of the experts in the field wanted to believe her findings,” said one of her collaborators, Steven Hinrichs, M.D., professor and chairman of the department of pathology and microbiology and director of the Nebraska Public Health Laboratory.
Finding an antidote to the stuff was a huge boon to rural medicine.
“Her internationally recognized career- long research efforts with BuChE provides the knowledge base needed to develop a safe and effective antidote to exposure to nerve agents, which are recognized as a military and civilian threat,” Dr. Lenz said.
Despite various international agreements, chemical weapons have been around — and used — for hundreds of years.
Nowadays you never know who might have them.
“Nerve agents are what they are worried about in Syria right now, because the Syrians still have a stockpile of nerve agents and it’s not sure how they’re going to maintain control of that,” Dr. Lockridge said.
But purified butyrylcholinesterase — via a single injection — will protect a person from these nerve agents for a week or two, Dr. Lockridge said.
The substance has undergone Phase 1 clinical trials to make sure it is safe for use on humans.
It is hoped that the work being done at UNMC will lead to further FDA approval for butyrylcholinesterase.
Dr. Lockridge credits Dr. Steve Hinrichs with making this particular UARC partnership work.
“I’m just a researcher,” she said. “He does all the things to make it happen.”
But she invented the process for making the stuff the military wants. Butyrylcholinesterase is present in what was once considered waste product after blood fractionation. Dr. Lockridge and her crew will extract and purify it using methods she developed.
While the “budget sequester” this spring has delayed funding, it is anticipated the project will begin later this summer. But all involved are hopeful that soon U.S. armed forces will be just a little bit safer, thanks to work being done at UNMC.