The National Institute of Neurological Disorders and Stroke (NINDS) Epilepsy Therapy Screening Program (ETSP)

Abstract

For over 40 years, the National Institute of Neurological Disorders and Stroke/National Institutes of Health-funded Anticonvulsant Screening Program has provided a preclinical screening service for participants world-wide that helped identify/characterize new antiseizure compounds, a number of which advanced to the market for the treatment of epilepsy. The newly-renamed Epilepsy Therapy Screening Program (ETSP) has a refocused mission to identify novel agents which will help address the considerable remaining unmet medical needs in epilepsy. These include identifying antiseizure agents for treatment-resistant epilepsy, as well as anti-epileptogenic agents that will prevent the development of epilepsy or disease-modifying agents that will ameliorate or even cure established epilepsy and its comorbidities. This manuscript provides an overview of the ETSP’s efforts aimed at identifying the next generation of therapeutic agents to further reduce the suffering from and burden of epilepsy.

Evaluation of antiseizure drug efficacy and tolerability in the rat lamotrigine‐resistant amygdala kindling model

“…While this model is useful for differentiation of potentially novel ASDs, 12 it should be noted that without repeated administration and testing it is difficult to interpret how these data will translate into clinical pharmacoresistant populations. Therefore, it is not clear whether the effects described herein would continue or change with repeated administration.…”

“…2 Further, it was observed that tolerance to lamotrigine extended to some sodium channel blockers but not to ASDs with other mechanisms. 12,13 One of the major goals for the development of novel ASDs is to minimize or eliminate side effects at therapeutic doses. 7,8 Further, resistance to one drug can extend to other ASDs, 5,6,10 thus suggesting the potential for this approach as a screening model for drug-resistant epilepsy.…”

“…The lamotrigine-resistant amygdala kindling model utilizes repeated administration of lamotrigine during the kindling process wherein animals develop a resistance to lamotrigine, which also extends to other some other ASDs. 12 At an early phase of preclinical drug evaluation, this approach is beneficial as it is inexpensive and informative for later studies. 12,13 One of the major goals for the development of novel ASDs is to minimize or eliminate side effects at therapeutic doses.…”

6 Hz Active Anticonvulsant Fluorinated N-Benzamide Enaminones and Their Inhibitory Neuronal Activity

“…Animal testing was performed in a manner consistent with a protocol approved by the Institutional Animal Care and Use Committee at the University of Utah (protocol 12-11011 and 15-10007, PI: Wilcox) [13,14,16,17,18]. …”

A companion to the preclinical common data elements for pharmacologic studies in animal models of seizures and epilepsy. A Report of the TASK3 Pharmacology Working Group of the ILAE/AES Joint Translational Task Force

“…In designing the CDEs and CRFs for pharmacologic studies for epilepsy, this Task Force focused on minimizing the overall burden on researchers who want to use CDEs while still promoting rigor and reproducibility. Herein, we outline the characteristics and components of sound pharmacologic research that are based, in a large part, on the success of the NINDS‐sponsored ETSP . For investigators wishing to evaluate investigational agents or pursue pharmacologic studies for specific patient populations, we encourage the implementation of these CRFs and CDEs with adjustments for the specific model at hand.…”