|Report from the ASP Working Group of the NANDS Council|
|American Epilepsy Society (AES)|
|John Kehne, Ph.D.
Recently the Anticonvulsant Screening Program has expanded screening capabilities through an HHS funded effort designed to search for counter measures to protect the world's populations against potential threats from intentional or accidental exposure to nerve agents.
Thus with funding provided to the NIH through HHS and the CounterACT Program the ASP has undertaken the development and validation of models, along with initiating a screening effort intended to identify, characterize and provide incentive for development of therapeutic agents for the prevention and treatment of neuronal damage resultant from exposure to nerve agents. One of the early manifestations of exposure to such agents is resistant seizures resulting in life-threatening status. The lithium-pilocarpine status epilepticus (SE) model is thought to closely recapitulate the pathophysiology of nerve agents that target acetylcholinesterase, the enzyme responsible for the metabolism of the neurotransmitter acetylcholine. In this regard, the pilocarpine model shares many characteristics with nerve agent-induced seizures which initially involve an overactivation of cholinergic receptors (Turski et al., 1989 ; McDonough and Shih, 1997). The ASP has employed a series of models designed to arrest benzodiazepine resistant SE including: pilocarpine induced status, neuroprotection against excitotoxins such as kainate or NMDA in in vitro hippocampal slice culture model, non-convulsive electrophysiology monitoring and isobolographic studies. These models were developed and incorporated into the ASP screening capabilities with the intent to find compounds useful against both convulsive and non-convulsive status. Active screening was initiated in February 2007 and already has resulted in several structurally novel preclinical leads. Although the NIH and the ASP do not screen against actual nerve agents we are uniquely positioned to facilitate potential linking of participants with successful compounds to other potentially interested parties that could provide further preclinical and even clinical development support.
All screening is undertaken in a blinded manner the same as compounds routinely submitted to the ASP. Data collection and distribution is confidential and otherwise handled the same as compounds traditionally submitted to the ASP Program.
Researchers interested in these services should contact ASP personnel for more detailed information on how to participate.
Last updated May 14, 2013