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Developmental and Epileptic Encephalopathies

Combining Behavioural, Electrophysiological, and Molecular Insights for Translational Neuropharmacology

At Ulysses Neuroscience Ltd., we offer a comprehensive preclinical platform for investigating Developmental and Epileptic Encephalopathies (DEEs). With facilities in Ireland (HPRA accredited) and North America (AAALAC accredited), we provide fully compliant environments for high-quality, ethically conducted in vivo studies.

What makes us unique is our integrated translational approach: we combine validated behavioural endpoints with physiological and molecular biomarkers and advanced sampling strategies, generating data with direct clinical relevance. Our platform bridges the gap between animal models and human studies, accelerating the path from compound to clinic.

Who will find this platform useful?

  • Pharma & biotech developing or repurposing compounds for DEEs and neurodevelopmental disorders

  • Researchers focused on epilepsy, DEEs and neurodevelopmental disorders

  • Clients enquiring translational EEG biomarkers to align preclinical results with clinical endpoints
  • Partners seeking integrated EEG + behaviour + biomarker data to support IND-enabling studies

Why partner with ULYSSES?

  • Accredited facilities in Ireland (HPRA) and North America (AAALAC).

  • Comprehensive portfolio of validated assays across behavioural domains.

  • Integration with EEG, PK/PD, biomarker, and histology capabilities.

  • Experienced neuroscientists guiding experimental design and data interpretation.

Overview of Preclinical DEEs Services

At Ulysses Neuroscience Ltd., we offer a comprehensive preclinical platform for DEEs, featuring our in-house mouse colonies. Our services include side-by-side phenotyping of male knockout (KO) and female heterozygous (Het) mice using an extensive behavioural test battery. This is complemented by advanced in vivo electrophysiology EEG recordings to support translational research and neuropharmacology programmes. For example, Ulysses Neuroscience Ltd. is the sole provider of a dedicated seizure assessment platform for a preclinical model of Cdkl5 Deficiency Disorder (CDD) that enables reproducible and translational evaluation of preclinical seizure susceptibility and anticonvulsive efficacy in Cdkl5 mutant mice. Our seizure platform is complemented by a comprehensive behavioral phenotyping platform, capturing all aspects of the DEE. Our in vivo studies are further strengthened by a validated, cross-species biomarker platform for both, mutant mice and patients, bridging preclinical and clinical endpoints.

Behavioral phenotyping assesses the main functional domains affected in DEEs through a combination of standardized behavioral and physiological assays:

Motor Function

  1. Open Field (Locomotor Activity): evaluates activity levels and exploratory drive
  2. Limb Clasping: measures motor coordination

Anxiety-like Behaviour

  1. Open Field (time in center zone): reflects anxiety and risk-avoidance behavior
  2. Elevated Plus/Zero Maze (EPM/EZM): assesses anxiety based on time spent in open versus closed areas

Cognition

  1. Y-Maze: evaluates spatial working memory and cognitive flexibility
  2. Novel Object Recognition (NOR): measures recognition memory and attention

Social Behaviour

  1. Three-Chamber Social Interaction Test: assesses sociability and social recognition
  2. Social Interaction Test (Open Field): measures direct social engagement, communication, and reciprocal social behaviors between freely interacting mice

Naturalistic Behaviour

  1. Marble Burying Test: measures repetitive and goal-directed behavior
  2. Nest Building Test: evaluates self-care, motivation, and motor ability
  3. Burrowing Test: assesses species-typical activity and general well-being

Electrophysiology

  1. EEG: monitors cortical activity, gamma oscillations, spectral power, and sleep architecture

Seizure Susceptibilty

  1. NMDA-Induced Seizures: evaluates seizure threshold, latency, and severity

Behavioural Phenotyping

CDKL5 Deficiency Disorder (CDD; Cdkl5 Mutant Mice) And Fragile X Syndrome (FXS; Fmr1-Ko Mice)

Phenotyping of CDKL5 mutant mice

Phenotyping of Fmr1-KO mice

Seizure Screening

  • Models: Fmr1-KO, Scn1a-KO, NMDA+Cdkl5-KO, MEST, 6 Hz, PTZ, kainate, chronic kindling, audiogenic seizures
  • Readouts: Seizure latency, frequency, severity, mortality
  • EEG: Wireless or tethered EEG with synchronized video enables precise seizure detection and classification
  • Pharmacology: Standard anti-seizure drugs and experimental therapeutics
Dedicated seizure assessment platform for Cdkl5-mutant mice.

Dedicated seizure assessment platform for Cdkl5-mutant mice. Adult male Cdkl5-KO and wildtype littermates were injected with NMDA and monitored immediately for 60 minutes. Seizure severity was scored using a modified Racine scale, with scores >3 classified as seizures. Cdkl5-KO mice displayed an increased susceptibility to NMDA-induced seizures, characterized by a shorter latency to onset, higher seizure scores, and 100% seizure incidence. Tissue was collected for subsequent biomarker analyses. Latency: Mann Whitney test, **p<0.01, median ± 95% CI. Seizure Score: Unpaired T-test, one-way ANOVA followed by Fisher’s LSD test; *p<0.05, mean ± SEM. n=5–6

per group.

PTZ seizure model in mice

Figure provided by Transpharmation.
Chemically induced seizure model using intravenous pentylenetetrazole (ivPTZ) infusion in mice. Intravenous PTZ infusion serves as a generalized seizure model that mimics aspects of absence (petit mal) seizures. In this model, the test compound is administered prior to the start of the PTZ infusion, and the seizure threshold is determined by calculating the total amount of PTZ required to elicit seizure activity (myoclonus, forelimb clonus, hindlimb tonus). Diazepam (2.5mg/kg, PO, upper row) is administered 60 min before the ivPTZ infusion as a positive control, and picrotoxin (2 mg/kg, IP, lower row) is administered 30 min prior as a reference convulsant. Unpaired T-test **p<0.01, ***p<0.001 vs Vehicle, n=11-12 per group. Data are shown as mean +- SEM.

EEG as Translational Biomarker

We incorporate high-resolution EEG telemetry and wireless platforms to capture disease-relevant network abnormalities and treatment responses, supporting:

  1. Pharmacodynamic profiling
  2. Sleep architecture and vigilance state analysis
  3. Electrophysiological biomarkers including gamma oscillations, spectral power shifts, and REM suppression

Available technologies include:

 

  1. Pinnacle Wireless Video-EEG
  2. DSI Telemetry
  3. Tainitec “TaiNi” head-mounted systems

Why EEG Matters in DEE Translational Research

In rodent DEE models, abnormalities in oscillatory activity, sleep patterns, and spectral power mirror patient EEG profiles and respond to CNS-active compounds. This makes rodent EEG a powerful pharmacodynamic biomarker to bridge preclinical and clinical development, support early go/no-go decisions, and de-risk novel neurotherapeutics.

Biomarker and Sampling Platforms

Ulysses is uniquely equipped to perform multiplexed biomarker analyses in tissues and fluids, alongside advanced cellular and histological profiling, using:

  1. Luminex 200
  2. MESO QuickPlex SQ 120MM
  3. Li-Cor Odyssey CLx
  4. Flow cytometry for neurogenesis and immune cell populations
  5. Histology, including Golgi staining and immunohistochemistry (IHC)

Validated Biomarkers in DEEs

  1. Neurodegeneration
    GFAP, Nf-L/Nf-H, Total Tau
  2. Neuroinflammation & Immunology
    IFN-α2a, IFN-β, IFN-γ, IL-6, IL-8, IL-13, IL-12/23p40, IL-23, CXCL10/IP-10, CCL2/MCP-1, CCL5/RANTES, CHI3L1 (YKL-40), LCN2, TNF-α
  3. Neuroplasticity & Synaptic Integrity
    BDNF, PSD-95, Synaptophysin, SV2A, Spinophilin
  4. Cytoskeletal Dynamics
    α-tubulin PTMs (acetylation, tyrosination/detyrosination)

Why Biomarker in Translational Research

Translating biomarkers from animal models to patient samples is essential to accelerating therapeutic development for DEEs such as CDKL5 Deficiency Disorder (CDD). By identifying molecular signatures conserved across species — such as elevated plasma acetylated α-tubulin, a proposed marker of dysregulated microtubule dynamics and impaired neurodevelopment — we gain powerful tools to track disease biology, stratify patients, and monitor drug response. These biomarkers offer objective, quantifiable endpoints that bridge preclinical and clinical studies, helping to de-risk compounds early and strengthen regulatory submissions.

Biomarker platform for Fmr1 mutant mice. Hippocampal tissue samples collected from Fmr1-mutant mice were analysed by infrared Western blot to quantify acetylated and total α-tubulin (Acet-Tub/Tot-Tub) levels and synaptic markers including PSD-95, Spinophilin, and Synaptophysin. Two-way ANOVA with sex (male, female) and genotype (WT, heterozygous, KO) as factors, *p<0.05, **p<0.01, ****p<0.0001 vs. male WT controls. +p<0.05; vs. WT females. #p < 0.05 vs. Fmr1-KO females. n=7-11 per group. Data are shown as mean ± SEM.

Translational biomarker platform for CDKL5 Deficiency Disorder (CDD). Plasma samples collected from Cdkl5-mutant mice were analysed by infrared Western blot to quantify acetylated and total α-tubulin (Acet-Tub/Tot-Tub) levels. The same assay was applied to plasma from CDD patients, revealing significant elevations in acetylated α-tubulin in both Cdkl5-mutant mice and patients. Unpaired t-test; *p<0.05, ***p<0.001, n=28–34 per group. Data are shown as mean ± SEM.

Publications

Behavioural benefits of GSK-3β inhibition and state-dependent microtubule signatures in the Fmr1-KO mouse

Kealy, J., Callaghan, C.K., Freeburn, A., Thornton, A., Greene, C., Garrone, B., Milanese, C. and Bianchi, M., 2025.

See the article

Frontiers in Neuroscience, 19, p.1643439.

Posters

Plasma biomarkers in CDKL5 Deficiency Disorder with focus on α-tubulin PTMs

See Poster

Jessica Pinto, Valentina Pergher, Enya Paschen, Connor Maltby, Massimiliano Bianchi

Download Our Capabilities

Biomarker

Cell Culture

Behavioural Assays

EEG in Rodents

DMPK

DEEs in Mice

Psychedelics Research

Depression Models

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