© 2026 Neurostrategix LLC.
February 02, 2026
Dentatorubral-pallidoluysian atrophy (DRPLA) is a fatal neurodegenerative disease arising from a CAG repeat expansion in the atrophin-1 (ATN1) gene. Because DRPLA, like many repeat expansion disorders (REDs), arises predominantly from toxic gain-of-function mechanisms, we hypothesized that ATN1 knockdown would have therapeutic potential. To test this, we established the first fully humanized mouse model of a RED, in which one allele of mouse Atn1 is completely replaced by human ATN1, including...
Read on PubMedDecember 11, 2025
Presenilin 2 (PSEN2) variants increase risk of Alzheimer's disease (AD) and unprovoked seizures. Yet, age-related PSEN2 contributions to seizure susceptibility are understudied. Critically, PSEN proteolytic capacity may regulate hippocampal kainate-type glutamate receptor (KAR) availability. Kainic acid (KA) is a KAR agonist that evokes severe seizures in mice. We hypothesized that PSEN2 knockout (KO) mice would show reduced latency to KA-induced seizures, increased seizure burden, worsened...
Read on PubMedOctober 09, 2025
Although advancements in epilepsy research have yielded new insights into pathophysiology and therapeutic targets, there is an ongoing need for new treatments to combat ongoing pharmacoresistance or offer disease-modifying effects. Variation between preclinical epilepsy research laboratories in methods of data capture, endpoint characterization, and experimental procedures may represent a significant challenge to finding consensus for new information important to the field. Harmonization of data...
Read on PubMedSeptember 18, 2025
Presenilin 2 (PSEN2) gene variants increase the risk of early-onset Alzheimer's disease (AD). AD patients with PSEN2 variants have increased risk of unprovoked seizures versus age-matched healthy controls, yet few studies have interrogated PSEN2 contributions to seizures, and fewer have done so with aging. PSEN2 variant mice also do not exhibit amyloid-β (Aβ) accumulation, allowing for the assessment of Aβ-independent contributions to seizure risk in AD. Critically, PSEN proteolytic capacity may...
Read on PubMedAugust 06, 2025
OBJECTIVE: Central to the development of novel antiseizure medications (ASMs) is testing of antiseizure activity in preclinical models. Although various well-established models exist, their predictive validity across the spectrum of clinical epilepsies has been less clear. We sought to establish the translational concordance of commonly used preclinical models to define models with the highest predictive clinical validity for focal onset seizures (FOS).
Read on PubMedJuly 19, 2025
Pharmaceutical-grade medium-chain triglycerides (MCTs) are common excipients for in vivo pharmacological studies in laboratory animals and as an experimental therapeutic in certain metabolic and neurologic disorders. In this study, we examined the tolerability of repeated administration of a pharmaceutical-grade formulation of 3 MCTs-caprylic, capric, and lauric acid-in mice via the oral and intraperitoneal routes. We administered either 8 or 4 µL of 100% MCTs or saline/gram of body weight...
Read on PubMedJuly 09, 2025
Antiseizure medications (ASMs) cause both acute and chronic behavioral side effects in individuals with epilepsy. While clinical and preclinical studies often focus on chronic effects, the acute dose-related impact of ASMs on behavior is underreported, especially in rodent temporal lobe epilepsy (TLE) models. Investigating the acute effects of both therapeutic and behaviorally impairing doses may predict clinically relevant adverse effects, such as sedation, hyperactivity, and impaired...
Read on PubMedJune 03, 2025
BackgroundAlzheimer's disease (AD) patients are at greater risk of focal seizures than similarly aged adults, which may accelerate cognitive decline. Older people with epilepsy generally respond well to antiseizure medications (ASMs). However, whether specific ASMs can differentially control seizures in AD is unknown. The corneal kindled model of chronic seizures allows for precisely timed drug administration studies to expediently evaluate efficacy and tolerability of investigational treatments...
Read on PubMedMarch 28, 2025
OBJECTIVE: Brain infection with Theiler's murine encephalomyelitis virus (TMEV) in C57BL/6J mice produces an etiologically relevant model of acquired seizures. Dietary changes can modify seizure presentation following TMEV brain infection and influence intestinal microbiome diversity and composition. Intestinal dysbiosis may thus similarly affect seizure burden and antiseizure medicine (ASM) activity in this model, independent of pharmacokinetic effects. We thus sought to define the influence of...
Read on PubMedMarch 15, 2025
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 is a deuterated analog of the ⍺2,3,5-selective GABA(A) receptor PAM L-838,417. The purpose of this study was to characterize the α-subunit selectivity of ENX-101 and evaluate its antiseizure potential in preclinical seizure and epilepsy models.
Read on PubMedJanuary 09, 2025
Seizures in people with Alzheimer's disease are increasingly recognized to worsen disease burden and accelerate functional decline. Harnessing established antiseizure medicine discovery strategies in rodents with Alzheimer's disease associated risk genes represents a novel way to uncover disease modifying treatments that may benefit these Alzheimer's disease patients. This commentary discusses the recent evaluation by Dejakaisaya and colleagues to assess the antiseizure and disease-modifying...
Read on PubMedDecember 09, 2024
Pharmaceutical-grade medium chain triglycerides (MCTs) are common excipients for in vivo pharmacological studies in laboratory animals, and as an experimental therapeutic in certain metabolic and neurological disorders. In this study, we examined the tolerability of repeated administration of a pharmaceutical-grade formulation of three MCTs-caprylic, capric, and lauric acid - in mice via the oral (PO) and intraperitoneal (IP) routes. We administered either 8 or 4 µL of 100% MCTs or saline/gram...
Read on PubMedNovember 18, 2024
Roughly 80% of the global burden of epilepsy resides in low- and middle-income countries (LMICs; WHO, 2022). Despite numerous new therapies for the treatment of epilepsy, the number of patients who remain resistant to available medications is unchanged. Additionally, no therapy has yet been clinically proven to prevent or attenuate the development of epilepsy in at-risk individuals. Unfortunately, access to next generation therapies in LMICs is low, the stigma associated with epilepsy remains...
Read on PubMed
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