A Funny Thing Happened on the Way to an Antidote PDF Print E-mail
A "failure" leads to success

Matthew Redinbo, Ph.D., and his team of scientists were very focused on their goal: to find a universal antidote that could thwart all possible nerve agents. The one-size-fits-all antidote could be taken by soldiers and first responders before they entered dangerous situations, protecting them from any nerve agents they might come across. The researchers made a number of tweaks to their favorite enzyme, successfully targeting it against one nerve agent after another. But they couldn’t find a way to target all of them at once.

Then they presented their frustrating findings at a meeting of biodefense experts, and a member of the audience raised his hand to offer a suggestion. Their approach, he explained, might not yield the universal prophylactic they were going for, but it could be used to detect and distinguish which nerve agent was present in a given area. They had just stumbled upon a “nerve gas fingerprint.”

“The person who raised his hand, he had been searching for this fingerprint technology,” said Redinbo, professor and chair of the department of chemistry at UNC-Chapel Hill. “We hadn’t even been thinking about that, because we were trying for a broad spectrum antidote. We hadn’t achieved what we wanted to achieve, and yet if you turn it a little bit, you find we have developed a great technology for something else.”

So Jon Edwards, a graduate student of Redinbo’s who had spearheaded aspects of the technology, did some digging and found that their approach was better than anything else that was currently available. The assays being used by the military were the same outdated ones from Vietnam. And because they almost always registered that a nerve gas was in the area, the soldiers tended to ignore them. What’s more, those tests only gave a yes or no answer.

“The problem is the antidotes are all different,” explained Redinbo. “If you have agent 1, you need antidote 1, but if you have agent 2, antidote 1 might kill you, but antidote 2 will help you. So there needed to be a way to quickly tell you it’s sarin, it’s cyclosarin, it’s soman – it’s this specific agent.”

After Edwards took the Launching the Venture course, offered by UNC’s Kenan-Flagler Business School with support from NC TraCS’s Carolina Kickstart and the Office of Technology Development, he and Redinbo decided to found their own company, Identizyme Defense Technologies. Carolina Kickstart, housed within the NC Translational and Clinical Sciences Institute – UNC’s home of the Clinical and Translational Science Awards -- facilitates and accelerates University startups through education, mentoring, funding and incubating companies spinning out of UNC-CH.

Redinbo's company, started with a $70,000 grant from the Army, is now looking for additional funds or partners to put the nerve gas fingerprint into a prototype that can undergo further testing.

“We figured the company was the best mechanism to get from the idea to the product,” said Redinbo. “Science is so self-perpetuating, it always asks more questions. A product should have an endpoint, a target where you see it has to end. At some point, you have to put a turbo charger under the commercial idea. And that has to separate, and it has a whole different trajectory.”

"That commercial idea stemmed from the basic science behind nerve gas, which does its damage by inhibiting acetylcholinesterase, an enzyme which is responsible for transmitting nerve signals throughout your body. When those nerve signals are blocked, everything in the body tenses up, eventually leading to death by suffocation. Antidotes that reactivate acetylcholinesterase should only be taken when a person is actually exposed to a specific agent, because otherwise it can cause their nerve cells to go into overdrive.

Identizyme’s device would be about the size of a credit card, containing each of the enzymes from their initial “failed” experiment. Each one of the enzymes reacts specifically with an individual nerve agent, creating a colorimetric or electronic readout that would be easy to interpret. Because each a specific spot or “lane” on the card would be labeled with its corresponding agent, users would know immediately if a yellow dot appears which nerve agent is present.

“Just think about what happened with the sarin nerve gas attack in the subway in Tokyo,” said Edwards, who is president of the company. “Most of the people that died in that incident were the first responders who went in to pick up the bag of nerve gas not realizing what it was, and they had massive doses of exposure. If they had our device, they could have gone in and wiped the floor and saw what they were dealing with, they could have gotten out and called in a Hazmat team better equipped to deal with the situation.“

So far the company’s approach continues to look far superior to the standard military assays. The researchers have tested their technology against all of the different agents that could have given them “false positives” such as floor wax, gasoline, sunscreen -- even blood, sweat and tears. Those are the very substances that can fool the current approaches into thinking a nerve gas is present, but not so with Identizyme’s approach.

Now Redinbo and Edwards are working to get the technology where it needs to be for the Department of Defense to fund it, or to catch the eye of one of the larger companies already established in the defense field to work on co-development. They could see the device being placed on Humvees, first responder’s uniforms, even lightposts throughout New York City, to warn of nerve gas in the air. But to get to that point, they need more money.

“Ten years ago this might have been easier, but now with this economy, it is a different world,” said Redinbo. “We are now the ones who have to bridge the gap from discovery to product, the ‘valley of death,’ because no one else will. Which means we will have to be willing to drive into the valley of death and have a lot of ideas die. You can’t be afraid to fail, because sometimes failure is the only way to success.”

By Marla Broadfoot
 

Carolina KickStart News & Reminders

Commercialization Award Recipients
Rounds 1 and 2:
Enci Therapeutics
G-Zero Therapeutics
Capture Pharmaceuticals
Hibernaid
Synereca Pharmaceuticals
X-in8 Biologicals Corporation

Rounds 4, 5 & 6:
Cell Microsystems
Ironwood Material Science
Cortical Metrics
Novolipid
LotusBioEFx
NeuroGate
Qualiber
Funding Deadlines
NSF STTR
December 2, 2011

HHS/NIH SBIR/STTR
December 5, 2011

Company Inception Loan (CIL)
NC Biotechnology Center

Deadline Rolling

The North Carolina Clinical and Translational Sciences (NC TraCS) Institute is one of 60 medical research institutions working together as a national consortium to improve the way biomedical research is conducted across the country. The consortium, funded through Clinical and Translational Science Awards (CTSA), shares a common vision to reduce the time it takes for laboratory discoveries to become treatments for patients, and to engage communities in clinical research efforts. It also is fulfilling the critical need to train a new generation of clinical researchers. The CTSA program is led by the National Center for Research Resources, part of the National Institutes of Health. For more information about NC TraCS programs and services, and the UNC-CH CTSA, call us at 919.966.6022, email us at nctracs@unc.edu, or visit us online at tracs.unc.edu