Wartime Organophosphate Exposure. Adenosine-based countermeasures to protect the CNS
Abstract
There have been numerous incidences of organophosphate (OP) nerve agents such as sarin (GB) being used as weapons, representing a significant threat to warfighters and civilians. Immediate effects of exposure can include seizures, respiratory distress and death (1). Beyond those first minutes, or following lower dose exposures, there is increased risk for brain injury that may progressively worsen for months post-exposure without resolution. (1). Collectively these CNS outcomes of OP exposure impact the long-term quality of life (QOL) for victims and could represent an immense burden on the VA health care system. Our recent DTRA-funded rodent studies suggest that adenosine augmentation effectively mitigates cognitive deficits and neuroinflammation elicited following irradiation, outcomes similar to those observed following OP exposure (preliminary data and 2,3). Our project, responsive to Thrust Area 7-Fundamental Science for Chemical and Biological Defense, develops a novel adenosine-based, neuroprotective countermeasure to combat adverse CNS outcomes following GB exposure. Our lead compound ABT-702, an adenosine kinase (ADK) inhibitor, is an orally available, potent, well-tolerated drug that can be stockpiled for emergencies. The principles by which this compound acts are approved by the FDA or are in phase I clinical trials for other applications (4). Our milestones will establish the impact of acute GB exposure on the CNS and the efficacy of ABT-702 to protect against or mitigate the adverse effects of OP exposure.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 08, 2022
- Source ID
- HDTRA12210044
Entities
People
- Janet Baulch
Organizations
- Defense Threat Reduction Agency
- University of California, Irvine