H. Steve White
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View article: Potential for Therapeutic Alteration of the Underlying Biology of Epilepsy
Potential for Therapeutic Alteration of the Underlying Biology of Epilepsy Open
Approximately 30–35% of people with epilepsy experience seizures despite taking antiseizure medications. Recurrent seizures that are independent of status epilepticus can be associated with neuronal injury and structural changes to the bra…
View article: Challenging the preclinical paradigm: Adverse effects of antiseizure medicines in male rats with drug‐resistant epilepsy
Challenging the preclinical paradigm: Adverse effects of antiseizure medicines in male rats with drug‐resistant epilepsy Open
Background and Purpose Drug‐resistant epilepsy affects 30% of patients who have uncontrolled seizures despite current antiseizure medications (ASMs). Preclinical drug screening often uses acute dosing and evoked seizures, which may not ful…
View article: PAC – A novel translational concordance framework identifies preclinical seizure models with highest predictive validity for clinical focal onset seizures
PAC – A novel translational concordance framework identifies preclinical seizure models with highest predictive validity for clinical focal onset seizures Open
/SUMMARY Objective Central to the development of novel antiseizure medications (ASMs) is testing of anticonvulsant activity in preclinical models. While various well-established models exist, their predictive validity across the spectrum o…
View article: <scp>ENX</scp> ‐101, a <scp> GABA <sub>A</sub> </scp> receptor α2,3,5‐selective positive allosteric modulator, displays antiseizure effects in rodent seizure and epilepsy models
<span>ENX</span> ‐101, a <span> GABA <sub>A</sub> </span> receptor α2,3,5‐selective positive allosteric modulator, displays antiseizure effects in rodent seizure and epilepsy models Open
Objective γ‐Aminobutyric acid type A (GABA A ) receptor positive allosteric modulators (PAMs) that lack α‐subunit selectivity, including benzodiazepines such as diazepam, exhibit antiseizure actions in animal models and in humans. ENX‐101 …
View article: A review of the putative antiseizure and antiepileptogenic mechanisms of action for soticlestat
A review of the putative antiseizure and antiepileptogenic mechanisms of action for soticlestat Open
Soticlestat (TAK‐935) is a potent and selective inhibitor of cholesterol 24‐hydroxylase (CYP46A1), an enzyme primarily expressed in the brain that catabolizes cholesterol to 24 S ‐hydroxycholesterol (24HC). In the ELEKTRA phase II clinical…
View article: A tribute to Arne Schousboe's contributions to neurochemistry and his innovative and enduring research in <scp>GABA</scp>, glutamate, and brain energy metabolism
A tribute to Arne Schousboe's contributions to neurochemistry and his innovative and enduring research in <span>GABA</span>, glutamate, and brain energy metabolism Open
This is a tribute to Arne Schousboe, Professor Emeritus at the University of Copenhagen, an eminent neurochemist and neuroscientist who was a leader in the fields of GABA, glutamate, and brain energy metabolism. Arne was known for his keen…
View article: Progress report on new medications for seizures and epilepsy: A summary of the 17th Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVII). II. Drugs in more advanced clinical development
Progress report on new medications for seizures and epilepsy: A summary of the 17th Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVII). II. Drugs in more advanced clinical development Open
The 17th Eilat Conference on New Antiepileptic Drugs and Devices took place in Madrid, Spain on May 5–8, 2024. As usual, the core part of the conference consisted of presentations on investigational drugs at various stages of development f…
View article: Progress report on new medications for seizures and epilepsy: A summary of the 17th Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVII). I. Drugs in preclinical and early clinical development
Progress report on new medications for seizures and epilepsy: A summary of the 17th Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVII). I. Drugs in preclinical and early clinical development Open
For >30 years, the Eilat Conference on New Antiepileptic Drugs and Devices has provided a forum for the discussion of advances in the development of new therapies for seizures and epilepsy. The EILAT XVII conference took place in Madrid, S…
View article: Development of a novel dosing paradigm to model diazepam rescue therapy in preclinical seizure and epilepsy models
Development of a novel dosing paradigm to model diazepam rescue therapy in preclinical seizure and epilepsy models Open
Diazepam is a cornerstone immediate‐use antiseizure rescue therapy that may extend the duration between seizure clusters in people living with epilepsy. However, our mechanistic understanding of intermittent rescue therapy on disease progr…
View article: Diet composition and sterilization modifies intestinal microbiome diversity and burden of Theiler's virus infection–induced acute seizures
Diet composition and sterilization modifies intestinal microbiome diversity and burden of Theiler's virus infection–induced acute seizures Open
Objective Brain infection with Theiler's murine encephalomyelitis virus (TMEV) in C57BL/6J mice can induce acquired epileptogenesis. Diet alters acute seizure incidence in TMEV‐infected mice; yet it is unclear whether intestinal dysbiosis …
View article: Temporal relationship between levetiracetam nonadherence and breakthrough seizures in a preclinical model of temporal lobe epilepsy
Temporal relationship between levetiracetam nonadherence and breakthrough seizures in a preclinical model of temporal lobe epilepsy Open
Objective Poor medication adherence remains a concern for individuals managing their epilepsy with antiseizure medicines (ASMs); however, ethical concerns around withholding medication make it impossible to study the causal relationship be…
View article: Diet composition and sterilization modifies intestinal microbiome diversity and burden of Theiler’s virus infection-induced acute seizures
Diet composition and sterilization modifies intestinal microbiome diversity and burden of Theiler’s virus infection-induced acute seizures Open
Objective Central nervous system infection with Theiler’s murine encephalomyelitis virus (TMEV) in C57BL/6J mice can model acquired epileptogenesis. Diet alters the acute seizure incidence in TMEV-infected mice; yet it is unclear whether i…
View article: New GABA-Targeting Therapies for the Treatment of Seizures and Epilepsy: I. Role of GABA as a Modulator of Seizure Activity and Recently Approved Medications Acting on the GABA System
New GABA-Targeting Therapies for the Treatment of Seizures and Epilepsy: I. Role of GABA as a Modulator of Seizure Activity and Recently Approved Medications Acting on the GABA System Open
γ-Aminobutyric acid (GABA) is the most prevalent inhibitory neurotransmitter in the mammalian brain and has been found to play an important role in the pathogenesis or the expression of many neurological diseases, including epilepsy. Altho…
View article: New GABA-Targeting Therapies for the Treatment of Seizures and Epilepsy: II. Treatments in Clinical Development
New GABA-Targeting Therapies for the Treatment of Seizures and Epilepsy: II. Treatments in Clinical Development Open
The inhibitory neurotransmitter γ-aminobutyric acid (GABA) plays an important role in the modulation of neuronal excitability, and a disruption of GABAergic transmission contributes to the pathogenesis of some seizure disorders. Although m…
View article: Perampanel’s forgiveness factor in a variable medication adherence paradigm in a rat model of chronic epilepsy
Perampanel’s forgiveness factor in a variable medication adherence paradigm in a rat model of chronic epilepsy Open
Background:Poor medication adherence contributes to increased morbidity and mortality in patients with epilepsy and may be under-addressed in clinical practice. Ethical concerns make it impossible to study the impact of medication nonadher…
View article: Animal Models of Drug-Resistant Epilepsy as Tools for Deciphering the Cellular and Molecular Mechanisms of Pharmacoresistance and Discovering More Effective Treatments
Animal Models of Drug-Resistant Epilepsy as Tools for Deciphering the Cellular and Molecular Mechanisms of Pharmacoresistance and Discovering More Effective Treatments Open
In the last 30 years, over 20 new anti-seizure medicines (ASMs) have been introduced into the market for the treatment of epilepsy using well-established preclinical seizure and epilepsy models. Despite this success, approximately 20–30% o…
View article: Soticlestat, a novel cholesterol 24-hydroxylase inhibitor, modifies acute seizure burden and chronic epilepsy-related behavioral deficits following Theiler's virus infection in mice
Soticlestat, a novel cholesterol 24-hydroxylase inhibitor, modifies acute seizure burden and chronic epilepsy-related behavioral deficits following Theiler's virus infection in mice Open
Temporal lobe epilepsy is the most common form of acquired epilepsy and can arise due to multiple inciting events, including central nervous system (CNS) infection. CNS infection with the Theiler's murine encephalomyelitis virus (TMEV) in …
View article: Anticonvulsive properties of soticlestat, a novel cholesterol 24‐hydroxylase inhibitor
Anticonvulsive properties of soticlestat, a novel cholesterol 24‐hydroxylase inhibitor Open
Objective The formation of 24 S ‐hydroxycholesterol is a brain‐specific mechanism of cholesterol catabolism catalyzed by cholesterol 24‐hydroxylase (CYP46A1, also known as CH24H). CH24H has been implicated in various biological mechanisms,…
View article: Continuous seizure emergency evoked in mice with pharmacological, electrographic, and pathological features distinct from status epilepticus
Continuous seizure emergency evoked in mice with pharmacological, electrographic, and pathological features distinct from status epilepticus Open
Summary Objectives Benzodiazepines are the standard of care for the management of sustained seizure emergencies, including status epilepticus (SE) and seizure clusters. Seizure clusters are a variably defined seizure emergency wherein a pa…
View article: Development of an antiepileptogenesis drug screening platform: Effects of everolimus and phenobarbital
Development of an antiepileptogenesis drug screening platform: Effects of everolimus and phenobarbital Open
Objective The kainic acid (KA)‐induced status epilepticus (SE) model in rats is a well‐defined model of epileptogenesis. This model closely recapitulates many of the clinical and pathological characteristics of human temporal lobe epilepsy…
View article: Continuous Seizure Emergency Evoked in Mice with Pharmacological, Electrographic, and Pathological Features Distinct from Status Epilepticus
Continuous Seizure Emergency Evoked in Mice with Pharmacological, Electrographic, and Pathological Features Distinct from Status Epilepticus Open
Summary Objectives Benzodiazepines are the standard of care for the management of sustained seizure emergencies, including status epilepticus (SE) and seizure clusters. Seizure clusters are a variably defined seizure emergency wherein a pa…
View article: Antiepileptogenesis and disease modification: Progress, challenges, and the path forward—Report of the Preclinical Working Group of the 2018 NINDS‐sponsored antiepileptogenesis and disease modification workshop
Antiepileptogenesis and disease modification: Progress, challenges, and the path forward—Report of the Preclinical Working Group of the 2018 NINDS‐sponsored antiepileptogenesis and disease modification workshop Open
Epilepsy is one of the most common chronic brain diseases and is often associated with cognitive, behavioral, or other medical conditions. The need for therapies that would prevent, ameliorate, or cure epilepsy and the attendant comorbidit…
View article: Diurnal burden of spontaneous seizures in early epileptogenesis in the post‐kainic acid rat model of epilepsy
Diurnal burden of spontaneous seizures in early epileptogenesis in the post‐kainic acid rat model of epilepsy Open
Patients with epilepsy can experience diurnal seizure patterns. However, few studies in rodent models of temporal lobe epilepsy (TLE) routinely quantify the diurnal pattern of spontaneous recurrent seizures (SRS), and those that have condu…
View article: The ups and downs of alkyl‐carbamates in epilepsy therapy: How does cenobamate differ?
The ups and downs of alkyl‐carbamates in epilepsy therapy: How does cenobamate differ? Open
Since 1955, several alkyl‐carbamates have been developed for the treatment of anxiety and epilepsy, including meprobamate, flupirtine, felbamate, retigabine, carisbamate, and cenobamate. They have each enjoyed varying levels of success as …
View article: Development of an Antiepileptogenesis Drug Screening Platform: Effects of Everolimus and Phenobarbital
Development of an Antiepileptogenesis Drug Screening Platform: Effects of Everolimus and Phenobarbital Open
Summary Objective The kainic acid (KA)-induced status epilepticus (SE) model in rats is an etiologically-relevant animal model of epileptogenesis. Just as in patients, who develop temporal lobe epilepsy (TLE) following SE, this rat model o…
View article: Progress report on new antiepileptic drugs: A summary of the Fifteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XV). I. Drugs in preclinical and early clinical development
Progress report on new antiepileptic drugs: A summary of the Fifteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XV). I. Drugs in preclinical and early clinical development Open
Since 1992, the Eilat Conferences have provided a forum for all stakeholders in the epilepsy community to appraise the latest data on new antiepileptic drugs and emergency seizure treatments, including, in recent years, updates on progress…
View article: Progress report on new antiepileptic drugs: A summary of the Fifteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XV). II. Drugs in more advanced clinical development
Progress report on new antiepileptic drugs: A summary of the Fifteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XV). II. Drugs in more advanced clinical development Open
The Fifteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XV) was held as a fully virtual conference from July 27 to July 30, 2020 for the sessions on drugs, and on August 3, 2020 for the sessions on devices. A total of …
View article: A multiorganism pipeline for antiseizure drug discovery: Identification of chlorothymol as a novel γ‐aminobutyric acidergic anticonvulsant
A multiorganism pipeline for antiseizure drug discovery: Identification of chlorothymol as a novel γ‐aminobutyric acidergic anticonvulsant Open
Objective Current medicines are ineffective in approximately one‐third of people with epilepsy. Therefore, new antiseizure drugs are urgently needed to address this problem of pharmacoresistance. However, traditional rodent seizure and epi…