Montclair, NJ. –David Rotella, the Montclair State University Sokol Professor of Chemistry and a former research scientist in the pharmaceutical industry, has been awarded a $2.5 million, five-year grant from the Defense Threat Reduction Agency (DTRA) to help develop inhibitors of the botulinum toxin, which causes botulism, a life-threatening illness characterized by paralysis and respiratory failure. Rotella is working with government agencies, pharmaceutical companies and other scientists to help the United States combat this serious threat in the war on bioterrorism.
“This is one of the most, if not the most, toxic agents known to man,” said David Rotella, Sokol Professor of Chemistry. It is also a potentially powerful bioterror weapon.
Rotella is participating in a consortium that includes the U.S. Army Institute for Chemical Defense, Brookhaven National Laboratory, the University of Massachusetts at Dartmouth, the Naval Research Laboratory and pharmaceutical companies Ossianix and Hawaii Biotech.
“The aim of the project is to identify a molecule or molecules that would provide either treatment for exposure to botulinum toxin, or provide prophylactic protection prior to exposure,” explained Rotella.
As Botox, botulinum toxin is injected in minute amounts into specific areas for localized effects. “But if you were exposed to this by food consumption or inhalation, a larger amount of the toxin would be more broadly distributed within you, which would lead to adverse, potentially fatal, results,” said Rotella.
Because the toxin is easily produced and easily distributed, it is a major bioterrorism concern. Following exposure, time becomes the enemy, as the physical effects begin shortly thereafter. To counter this, an effective drug would need to be readily available for rapid administration in the event of a widespread exposure to the toxin. Developing a drug that could be administered prior to exposure that would provide protection is also a possibility, Rotella said.
Each member of the consortium brings different skills to this large-scale, long-term project. Rotella’s team, which includes a post-doctoral scientist, is working to synthesize new molecules – or inhibitors -- that are potential drug candidates and that will be evaluated as part of the program. “These aren’t drugs per se,” he noted. “These are molecules with properties that might inhibit the enzyme botulinum A protease that we hope to improve, so that at least one compound could eventually be available for use in humans.
“We have made a number of compounds that are undergoing evaluation at Montclair State and with our collaborators,” said Rotella.
John Siekierka, Montclair State chemistry and biochemistry professor and director of the University’s Margaret and Herman Sokol Institute for Pharmaceutical Life Sciences, is also involved in preliminary testing.
“In case botulinum toxin is used as a bio-weapon, it is important to have a safe treatment for exposure,” he said. “My lab is testing potential drug candidates on normal human liver cells to determine if they are safe.”
If a molecule kills human cells, it would be immediately ruled out as a potential drug candidate.
Pleased with the progress so far, Rotella said, ““We are improving the properties of our starting points and will work hard with the consortium to meet our goal.”
Rotella is participating in a consortium that includes the U.S. Army Institute for Chemical Defense, Brookhaven National Laboratory, the University of Massachusetts at Dartmouth, the Naval Research Laboratory and pharmaceutical companies Ossianix and Hawaii Biotech.
“The aim of the project is to identify a molecule or molecules that would provide either treatment for exposure to botulinum toxin, or provide prophylactic protection prior to exposure,” explained Rotella.
As Botox, botulinum toxin is injected in minute amounts into specific areas for localized effects. “But if you were exposed to this by food consumption or inhalation, a larger amount of the toxin would be more broadly distributed within you, which would lead to adverse, potentially fatal, results,” said Rotella.
Because the toxin is easily produced and easily distributed, it is a major bioterrorism concern. Following exposure, time becomes the enemy, as the physical effects begin shortly thereafter. To counter this, an effective drug would need to be readily available for rapid administration in the event of a widespread exposure to the toxin. Developing a drug that could be administered prior to exposure that would provide protection is also a possibility, Rotella said.
Each member of the consortium brings different skills to this large-scale, long-term project. Rotella’s team, which includes a post-doctoral scientist, is working to synthesize new molecules – or inhibitors -- that are potential drug candidates and that will be evaluated as part of the program. “These aren’t drugs per se,” he noted. “These are molecules with properties that might inhibit the enzyme botulinum A protease that we hope to improve, so that at least one compound could eventually be available for use in humans.
“We have made a number of compounds that are undergoing evaluation at Montclair State and with our collaborators,” said Rotella.
John Siekierka, Montclair State chemistry and biochemistry professor and director of the University’s Margaret and Herman Sokol Institute for Pharmaceutical Life Sciences, is also involved in preliminary testing.
“In case botulinum toxin is used as a bio-weapon, it is important to have a safe treatment for exposure,” he said. “My lab is testing potential drug candidates on normal human liver cells to determine if they are safe.”
If a molecule kills human cells, it would be immediately ruled out as a potential drug candidate.
Pleased with the progress so far, Rotella said, ““We are improving the properties of our starting points and will work hard with the consortium to meet our goal.”
