Led by Aristea Galanopoulou, MD, PhD , and Solomon L. Moshé, MD , the Montefiore Einstein Laboratory of Developmental Epilepsy advanced several major research initiatives in 2025 aimed at transforming the understanding and treatment of developmental and epileptic encephalopathies (DEEs). A significant focus was on infantile spasms, or infantile epileptic spasms syndrome (IESS), where the team continues to lead in developing novel therapeutics and sophisticated preclinical models that accelerate progress toward targeted, more effective treatments for infants and young children with these complex conditions. Collectively, these studies demonstrate a comprehensive approach to understanding and treating pediatric epilepsy syndromes, using advanced modeling techniques to facilitate therapeutic discovery.

DEEs are a heterogeneous group of conditions marked by early-onset, often severe epileptic seizures, characteristic electroencephalography (EEG) abnormalities, and significant neurodevelopmental impairment. Infantile spasms, or IESS, is among the most severe forms of DEE, associated with epileptic spasms and poor neurodevelopmental outcomes.

The research team recently published the 2025 updates in Epilepsia Open and Epilepsy & Behavior on the multiple-hit model of IESS, a preclinical model of structural etiology and drug-resistant IESS that has been optimized for screening new therapeutic candidates. In this work, the team expanded the model’s pharmacosensitivity characterization by evaluating the efficacy and tolerability of several emerging agents, including celastrol and anti-inflammatory and immunomodulatory drugs such as fingolimod and sivelestat. The findings further establish the model as a critical platform for therapeutic discovery and deepen understanding of key neurobiological pathways, including inflammatory and immune-related processes, oxidative stress, and NF-κB and mTOR signaling.

The team’s commitment to translational science is further demonstrated by ongoing work in 2025 evaluating the efficacy and tolerability of a novel small-molecule selective activator of Kv7.2/7.3 potassium channels in infantile spasms, a project sponsored by Biohaven. BHV-7000 is also being explored as a potential therapy for KCNQ2-associated DEE. In addition, Montefiore Einstein is a key site for two active Phase 2/3 multicenter, randomized, double-blind, placebo-controlled clinical trials evaluating BHV-7000 in adults with refractory focal onset epilepsy and as adjunctive therapy in adults with idiopathic generalized epilepsy with generalized tonic-clonic seizures, with open-label extension. This work complements the Laboratory’s preclinical efforts and underscores Montefiore Einstein’s commitment to advancing next-generation epilepsy therapies.

Furthermore, the Laboratory contributed to a series of recent appraisals for the Workshop on Neurobiology of Epilepsy (WONOEP), published in late 2024 and 2025, addressing key emerging areas in early-onset epilepsies. These appraisals examined targeted therapy development, advances in modeling and genetics, the role of glial cells in focal malformations, and broader perspectives on the immunopathogenesis of epilepsy. Together, this work is helping to shape the evolving landscape of precision therapeutics for early-life epilepsies.

“By integrating advanced modeling techniques with clinical investigation, we are deepening the understanding of pediatric epilepsy syndromes and helping to accelerate therapeutic discovery for some of the most complex and challenging epilepsies,” said Dr. Galanopoulou. “Our goal is to develop treatments that can meaningfully change long-term outcomes for children with developmental epileptic encephalopathies.”

Together, these initiatives underscore Montefiore Einstein’s commitment to advancing scientific discovery and improving outcomes for children with the most severe early-onset epilepsies. Montefiore Einstein is ranked in the top 1% of hospitals nationwide for neurology and neurosurgery by U.S. News & World Report and is home to one of the first Comprehensive Level 4 Epilepsy Centers, the highest designation from the National Association of Epilepsy Centers.

Publications

Galanopoulou AS, Mowrey WB, Liu W, et al. The multiple-hit model of infantile and epileptic spasms: The 2025 update. Epilepsia Open. Published online October 14, 2025. doi:10.1002/epi4.70158

Shandra O, Wang Y, Coles LD, et al. Efficacy and tolerability of celastrol and edaravone in the multiple-hit rat model of infantile spasms. Epilepsy & Behavior. 2025;162:110159. doi:10.1016/j.yebeh.2024.110159

Casillas-Espinosa PM, Wong JC, Grabon W, et al. WONOEP appraisal: Targeted therapy development for early onset epilepsies. Epilepsia. 2025;66(2):328–340. doi:10.1111/epi.18187

Quatraccioni A, Cases-Cunillera S, Balagura G, et al. WONOEP appraisal: Genetic insights into early onset epilepsies. Epilepsia. 2024;65(11):3138–3154. doi:10.1111/epi.18124

De Meulemeester AS, Reid C, Auvin S, et al. WONOEP appraisal: Modeling early onset epilepsies. Epilepsia. 2024;65(9):2553–2566. doi:10.1111/epi.18063

Cases-Cunillera S, Quatraccioni A, Rossini L, et al. WONOEP appraisal: The role of glial cells in focal malformations associated with early onset epilepsies. Epilepsia. 2024;65(12):3457–3468. doi:10.1111/epi.18126

Çarçak N, Al Maawal S, Thergarajan P, et al. WONOEP XVII appraisal: The immunopathogenesis of epilepsy. Epilepsia. Published online November 22, 2025. doi:10.1111/epi.70027

Clinical Trials

A Study to Determine if BHV-7000 Is Effective and Safe in Adults with Idiopathic Generalized Epilepsy with Generalized Tonic-Clonic Seizures (SHINE)

ClinicalTrials.gov identifier: NCT06425159

Study to Determine if BHV-7000 Is Effective and Safe in Adults with Refractory Focal Onset Epilepsy (RISE 3)

ClinicalTrials.gov identifier: NCT06309966