Overview
The mission of the NINDS Epilepsy Therapy Screening Program (ETSP) is to facilitate the discovery of new therapeutic agents that address the unmet medical needs in epilepsy. 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 focused on addressing drug resistant epilepsy, disease prevention and modification. 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. 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 rodent epilepsy and 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), retigabine (Potiga), cannabidiol (Epidiolex) and cenobamate (Xcopri).
Description of Testing Services
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 over 30,000 compounds to determine if the compound has been tested previously. Accepted compounds are then evaluated in assays from specific flowcharts (such as the drug resistant epilepsy flowchart). 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.
Over 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 the ETSP's 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.
How to Participate
Those interested in participating should contact Brian Klein, PhD for more information and to discuss research goals, resources, and timelines. This process will typically begin with an introductory meeting with the NINDS ETSP team. A signed confidentiality agreement between the NINDS and each potential participant is required before submission of compounds for evaluation. For compounds approved for testing in the program, preliminary screening is normally performed using in vivo rodent models, thus an initial sample size of approximately 350 to 500 mg is required, unless prior knowledge of the compound's efficacy and toxicity is available which can better define the expected dose range needed. Directions for packaging and compound submission will also be provided prior to sample shipment.
Confidentiality
NINDS recognizes the importance of confidentiality to the success of the ETSP and its participants. Participation in the ETSP begins only after the appropriate representatives from both the participant's organization and the NINDS sign the confidentiality agreement. This document defines the legal parameters for the partnership. All screening and other communication activities are performed in strict confidence to help safeguard the participant's intellectual property. Chemical structures are considered proprietary unless otherwise specified by the supplier. The only testing undertaken by the ETSP is that agreed upon by participants in collaboration with ETSP personnel. To further assure confidentiality, each newly submitted compound is assigned a unique ETSP number code to be used in communications, tracking, and analysis. Screening personnel are blinded to both the structure and the source of submitted compounds, and screening results are provided exclusively to the participating supplier unless otherwise authorized.
External Consultant Board
The External Consultant Board (ECB) was established in 2015 to provide feedback on the ETSP direction, testing strategy and models and workflows in development. The ECB was established based on recommendations from the 2015 report prepared by a Working Group of the National Advisory Neurological Disorders and Stroke (NANDS) Council following a review of the ETSP. The ECB members are internationally recognized leaders in epilepsy research and bring unique perspective as physician scientists, industry and academic researchers, and patient advocacy. They collectively provide expertise in basic, translational, and clinical research, clinical practice, and drug development. The ETSP meets with the ECB panel biannually to discuss the program’s progress, proposed changes to testing strategy and new directions. However, individual ETSP participants and their project’s data are confidential and are not shared or discussed with the ECB members.
Amy Brooks-Kayal, MD
Chair and Professor
Department of Neurology
University of California, Davis
Jennifer Kearney, PhD
Associate Professor
Department of Pharmacology
Northwestern University Feinberg School of Medicine
Henrik Klitgaard, PhD
Vice President
UCB Biopharma SPRL, Braine-I’Alleud
Wolfgang Löscher, DVM, PhD
Professor
Department of Pharmacology, Toxicology, and Pharmacy
University of Veterinary Medicine and Center for Systems Neuroscience, Hannover
Laura Lubbers, PhD
Chief Scientific Officer
CURE Epilepsy
James McNamara, MD
Professor of Neurobiology, Neurology, and Pharmacology
Director, Center for Translational Neuroscience
Duke University School of Medicine
Resources and Tools
News & Events
Upcoming events attended by ETSP staff
Park City Epilepsy Meeting
October 15 - 17, 2023, Park City, UTNINDS ETSP Open House at the University of Utah contract testing site
10:00 AM - 1:00 PM on October 18, 2023, Salt Lake City, UT
To attend the free Open House and learn about the program’s testing and meet the NINDS and testing site staff please email ETSP Director Brian.Klein@nih.govAmerican Epilepsy Society (AES) Annual Meeting
December 1- 5, 2023, Orlando, FL
Contacts
Brian Klein, PhD | Program Director
Brian.klein@nih.gov
Yogendra Raol, PhD | Scientific Project Manager
yogendra.raol@nih.gov
Shalini Sharma, M.S.B. | Scientific Project Manager, Medicinal Chemist
Shalini.sharma@nih.gov
Dhananjaya Kempegowda, B.Eng. | Data Scientist Engineer
dhananjaya.kempegowda@nih.gov
Lekyla Whitaker | Operations Coordinator
lekyla.whitaker@nih.gov
Related Topics
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 or program data subsequently published by the participant. PANAChE is also a repository for information on the animal models and assays currently or historically used in the ETSP.
ETSP Compound Registration and Test Report Web Portal (registration required)
Reports on the ETSP (2020) and ASP (2015 & 2012) from NANDS Council Working Groups
- May 2020(pdf, 357 KB)
- May 2015
- February 2012