This technology is a series of non-oxime molecules that prevent damage to the acetylcholinesterase enzyme following exposure to organophosphate compounds (OPCs), thereby extending the window for successful treatment of OPC toxicity.
Exposure to organophosphate compounds (OPCs), a class of chemical warfare agents, causes neurotoxicity due to the agents’ covalent binding and inhibition of the acetylcholinesterase (AChE) enzyme. Without prompt reactivation of AChEs through administration of oxime compounds, the resulting AChE adducts undergo subsequent rearrangements that result in irreversible aging of the enzyme. In view of the short window of opportunity for oxime administration following OPC exposure, there remains a need for the development of molecules that counteract AChE aging in order to extend the period for successful treatment of OPC toxicity.
This technology describes a series of non-oxime molecules, including small molecules, antibodies, and irreversible crosslinkers, that crosslink with acetylcholinesterase (AChE) to prevent aging following exposure to organophosphate compounds (OPCs). Treatment of AChE with the crosslinking agents prevents the inactivation of the enzyme, even in the absence of a reactivating compound, allowing for spontaneous reactivation of the enzyme. Following treatment with the crosslinking agents, AChE retains enzymatic activity for up to two weeks following OPC exposure. As such, this technology has the potential to extend the window for treating OPC toxicity.
This technology has been demonstrated to confer resistance to AChE aging in vitro.
IR CU20110
Licensing Contact: Jerry Kokoshka