|Reports on the ASP from NANDS Council Working Groups|
|John Kehne, Ph.D.
|Meetings and Conferences|
The mission of the NINDS Epilepsy Therapy Screening Program (ETSP) is to encourage and facilitate the discovery of new therapeutic agents for the treatment of epilepsy disorders. The program provides opportunities for researchers from academia and industry in the U.S. and abroad to submit compounds for screening in a battery of well-established rodent seizure models. These tests are performed at a contract facility based at the University of Utah on a blinded and confidential basis and at no cost to the ETSP participants. The NINDS ETSP staff reports test results to participants and provides advice on next steps for promising compounds. Since its establishment in 1975, the program has made important contributions to the development of several FDA-approved drugs for epilepsy, including felbamate (Felbatol), topirimate (Topamax), lacosamide (Vimpat), and retigabine (Potiga). Historically, the ETSP has focused on identifying symptomatic treatments for seizure disorders, but based on recent recommendations from working groups of the National Advisory Neurological Disorders and Stroke (NANDS) Council, the program is placing emphasis on refractory epilepsy, epileptogenesis and disease progression, special epilepsy populations, and epilepsy comorbidities. Other key recommendations implemented include forming an External Consultant Board (ECB) to provide regular feedback to the ETSP and changing the name of the program to reflect the emphasis on identifying differentiated agents to address the unmet medical needs of epilepsy.
A web-based research tool called PANAChE (Public Access to Neuroactive & Anticonvulsant Chemical Evaluations) provides open access to nonproprietary chemical structures and biological data for compounds previously screened in the ETSP, including antiseizure drugs (ASDs) as well as drugs used for other indications. This database is being populated beginning with known drugs in the public domain and only those ETSP compounds that are approved by the participant. PANAChE is also a repository for information on the animal models and assays currently or historically used in the ETSP.
Evaluation of a submitted compound for suitability for testing in the ETSP begins with an assessment of the compound’s biological and chemical rationale that includes a structural comparison within an internal program database of approximately 32,000 compounds to determine if the compound has been tested previously. Accepted compounds are then evaluated in assays whose sequence is described in specific flow charts (such as, a flow chart for drug refractory epilepsy). Each stage of evaluation occurs with NINDS ETSP staff consultation with the participant. The ETSP provides feedback on results and an assessment of the potential success of each particular compound or compound class.
Given the forty year history of the ETSP, the models in use have evolved over time such that new assays have been added to the program and others have been discontinued. See HOME on the PANAChE website for a description of all models and tests used, both currently and historically, in the ETSP. The site also describes the specific flow charts currently used for compound evaluation.
Last Modified March 24, 2016