PEG-MODIFIED ENZYMES FOR IN-VIVO DECON OF OP TOXINS

DESCRIPTION (provided by applicant): Agentase, LLC seeks follow-on Phase II Small Business Innovation Research funding to develop prototype formulations of chemically modified enzymes for the treatment and, more importantly, the prevention of organophosphorus poisonings. Several known enzymes exhibit hydrolytic activity on target organophosphorus compounds including nerve agent chemical weapons such as sarin and soman as well as many commercially available pesticides, including parathion, methyl parathion and chlorpyrifos. Many of these enzymes have been derived from bacterial sources and are unfortunately not conducive to use as an in-vivo medical treatment for a variety of reasons including acute antigenicity, poor enzyme stability, and brief in-vivo residence times. When one considers that annually 3 million cases of severe poisoning and 220,000 deaths worldwide are associated with OP pesticides, there are obviously unmet needs associated with their use. There is a clear need for technology capable of protecting individuals from overexposure to OP compounds. Successful Phase I research has demonstrated that the concept of protecting a person from an otherwise debilitating dose of OP toxins with chemically modified enzyme is viable. Modified OP hydrolyzing enzymes have potential utility as medical treatments for exposed individuals as well as preventative security for individuals at high risk of OP exposure. Such treatments have potential utility at hospitals, agricultural sites employing OP pesticides, civil defense treatment centers for chemical terrorism, and with the armed forces. Research will also be extended to other model systems of clinical relevance.