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UNC-linked research team has strategy to combat pesticide, nerve-agent poisonings

CHAPEL HILL A UNC-Chapel Hill scientist and his research partners in Russia think they’ve hit on a technique that could eventually prevent or mitigate poisonings from some of the most potent pesticides and nerve agents known to man.

The team, led by Eshelman School of Pharmacy professor Alexander “Sasha” Kabanov, reported its findings via a journal article first published on the internet at the end of 2016. But they began receiving wider notice this spring, fueled by Russian media attention and the official suspicion in Malaysia that two assassins used VX nerve agent in February to kill the half-brother of North Korean leader Kim Jon Un.

Kabanov, however, has his eyes fixed firmly down the road.

“It’s not only a weapon and not only terrorism. It’s also several hundred thousand fatalities due to pesticide poisoning across the world,” he said, alluding to the family of chemicals that includes VX, paraoxon and parathion. “So it’s a major problem for world health. Having an inexpensive and preventive and not drastic [counter] measure would be a good thing.”

The strategy capitalizes on an idea Kabanov has pursued throughout a career that began in Russia, at M.V. Lomonosov Moscow State University, and continued in the U.S. in faculty posts at the University of Nebraska and UNC.

He believes and has shown, via numerous published research papers, that it’s possible to use “micelles” — solutions that include nanoparticles — to speed the delivery of medically useful enzymes to the body. Kabanov and his colleagues have looked for applications in fighting cancer, Parkinson’s Disease, strokes and other “devastating human diseases.”

About six years ago, they decided to also look into whether the idea can be used to counter toxic “organophosphates,” the name for the family of phosphorus and carbon-based compounds that includes insecticides and nerve agents.

The resulting paper, published in the Journal of Controlled Release, reported on experiments with rats conducted in Russia, and some follow-up checks with mice that occurred in Chapel Hill.

The Russian end of the project involved treating rats with a particular type of of enzyme known to break down the toxins, but that on its own has trouble lasting long enough to do much good.

“The problem is it’s not terrifically stable, during storage and also during injection into the body,” Kabanov explained. “It’s rapidly eliminated; there’s an immune response. So the idea was to use this technology, which allows us to encapsulate it by mixing two solutions. That results in a change of the properties. By doing that, first we increase stability — we can keep it in the refrigerator for, say, two years with little loss of activity. More importantly, it increases the circulation in the body.”

According to the paper, there were two sets of rat experiments. One involved paraoxon, a component of the insecticide parathion. Some rats received a dose of known to be large enough on average to kill half of them. Results-wise, the enzyme treatment “abolished all signs of intoxication and prevented [the] death of all injected animals,” the team said.

It also seemed to inoculate the rats against the effects of the poison, for up to 17 hours ahead of time.

The second set of rat experiments involved VX, the nerve weapon allegedly used in the successful attack on Kim Jong Nam, the half brother of Kim Jon Un.

It took help from a research institute linked to the Russian defense ministry and found that the 30-minute survival rates for a known lethal dose of the agent improved from 50 percent, to 75 percent or 83.3 percent depending on the electrical charge of the enzyme solution. Some of the rats survived for up to seven days, though all were eventually euthanized.

Kabanov, now a naturalized U.S. citizen, originally trained at Moscow State as chemist and renewed his ties to it in 2010 when he applied for and won a “mega-grant” it offered in hopes of convincing Western scientists to establish labs there. UNC inherited the relationship with his Moscow-based Laboratory of Chemical Design of Bionanomaterials when it recruited him from Nebraska in 2012.

“We were applying our American technology, of Russian origin, which obviously became global because there are so many people working in this field,” he said.

In addition to possible human-health benefits, the idea has potential veterinary applications, as livestock can and does die from pesticide exposure, Kabanov said. And while “from the practical standpoint it seems rather straightforward,” there’d be a lot of research and regulatory hurdles to overcome before it could be put to use.

Ray Gronberg: 919-419-6648, @rcgronberg

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