Finding the antidote: MSU researcher pursues breakthrough in nerve agent remedy

As a Giles Distinguished Professor, Jan Chambers has helped a generation of MSU students gain knowledge and experience in the laboratory as she pursues groundbreaking research on nerve agent antidotes.

The blood-brain barrier might no longer stand in the way of preventing the long-term effects of nerve agents as research out of Mississippi State University works to push an antidote through this long-standing obstacle.

Jan Chambers, who is a Giles Distinguished Professor, and her research team have spent several years making and testing nerve agent antidotes that have the potential to cross the blood-brain barrier, the highly selective membrane that prevents many drugs in the circulating blood from entering the brain and the rest of the central nervous system. Currently, approved nerve agent antidotes protect the heart, lungs and other vital organs, but the antidote Chambers is developing aims to cross the blood-brain barrier to protect victims from seizures and brain damage.

“If the brain experiences prolonged seizures, cells are killed and that causes permanent brain damage,” Chambers explained. “The brain just doesn’t repair itself as well as most other tissues. If you survive the event, you may still have lifelong consequences because of the brain damage.

“We’re trying to develop antidotes that might replace or be used in conjunction with the currently approved antidote, so we can get an antidote into the brain and dampen down some of the toxic action to prevent or at least attenuate the brain damage.”

As director of the College of Veterinary Medicine’s Center for Environmental Health Sciences, Chambers leads a team of research faculty, associates and technicians, as well as graduate and undergraduate students to develop an antidote they hope no one ever has to use.

The idea is that those in combat could carry the antidote with them if they are likely to enter an area where sarin gas has been released. Emergency officials could build a strategic reserve of the antidote in case of a terrorist attack using nerve agents such as sarin or VX, or if a terrorist makes a threat agent from some high potency insecticides. Because of the significant potential military and societal benefit of an improved antidote, Chambers has received research funding from the U.S. Department of Defense and the National Institutes of Health.

“We have some surrogate chemicals we study that resemble VX and sarin,” Chambers said. “Our antidotes are showing therapeutic efficacy with both of those, which is encouraging.”

Instead of using the nerve agents themselves, Chambers uses the safer surrogate compounds to study the effectiveness of the antidote in her lab. The antidotes that show greater potential are tested in labs elsewhere that are authorized to use nerve agents for research. Recent tests have shown promising results, Chambers said.

“The path forward is developing information on how long the antidote will be effective in the body, determining if it is toxic in its own right or how much a human can tolerate without showing any adverse effects, and how it works against other types of agents besides the ones we’re studying,” Chambers explained. “That’s the type of information we would have to supply to the FDA. Our perspective is to try not just to save the life, but to save the brain, too, to allow the person who is exposed to this type of chemical the hope of a normal life after that event.”

LEFT: Jan Chambers leads a staff of full-time, graduate and undergraduate researchers at the College of Veterinary Medicine’s Center for Environmental Health Sciences. RIGHT: Chambers spent many years collaborating on research projects with her husband Howard before he died in 2016. (Photo submitted)

Chambers, whose work has usually focused on pesticide toxicology, said she never expected to be developing a drug. The opportunity came when she and her late husband, Howard, met with a former student who was working for the U.S. Air Force in 2010. A renowned toxicologist with a chemical background, Howard sketched out his ideas for the antidote compounds on a napkin at a local restaurant, and eventually funding was secured for the research.

Chambers admitted she also did not expect to spend so long in Starkville when she made the move from her native state of California with Howard in the 1970s. She earned a doctorate in animal physiology from MSU in 1973, joined the faculty ranks in 1980, and has gone on to serve as a principal investigator of approximately $30 million in federally funded grants for the university. Among many honors and distinctions, she is a Diplomate of the American Board of Toxicology, Fellow of the Academy of Toxicological Sciences and in 2017 received a Southeastern Conference Faculty Achievement Award.

Jan and Howard collaborated on many research projects over the years, including the nerve agent antidote research. Following Howard’s death in 2016, Jan established an endowed undergraduate scholarship in his memory at MSU.

She also continues Howard’s legacy by moving forward with the nerve agent antidote research. Howard is the author on a patent for the testing compounds, along with Jan and lab manager Eddie Meek.

“If it hadn’t been for Howard drawing out that chemical and having a chemical in mind, we wouldn’t be where we are today,” Chambers said. “I was more the biologist of the team and he was the chemist. He was always thinking, ‘Wouldn’t it be so cool if we got a superior antidote on the market?’ As long as the data looks good and we can continue to secure a funding stream, I’m just pursuing what we invented.”

Story by James Carskadon, Photos by Megan Bean & Tom Thompson