TAUOPATHY - DRAFT
Overcoming MTLE Condition:
a Major Challenge for Preclinical Epilepsy
With over 10% of the total Epilepsy population affected, Mesial Temporal Epilepsy (MTLE) – or Focal Epilepsy – is a major challenge for patients, as most pharmacological treatments have no effect on these seizures. Despite the availability of over 20 antiseizure medications, about one-third of epilepsy patients remains drug resistant representing an important unmet medical need.
There are several models in epilepsy for drug makers to test their compounds, but not all models are equal and adapted for the MTLE condition, which is a non-convulsive form of Epilepsy. For drug developers, using the right non-convulsive model that perfectly mimics human MTLE at the preclinical stage is key to accurately assess the efficacy of their drug candidates.
SynapCell's EEG Biomarker & MTLE Model for Focal Epilepsy: A Powerful Combination for Assessing Efficacy Testing
Our in vivo EEG Biomarker approach is what makes SynapCell unique. Models proposed in our portfolio express translational EEG biomarkers that are identical to the ones found in human. Our MTLE model and its related EEG biomarker (HPD – Hippocampal Paroxysmal Discharges) are a powerful combo that delivers smooth and relevant human-rodent translation, high reproductibility levels and robust endpoints. This duo is particularly well-suited to evaluate compounds effects for Focal Epilepsy with no bias and can predict the impact that a molecule may have through the different clinical phases.
SynapCell's MTLE Model Perfectly Mimics Human MTLE
Our MTLE mouse model mirrors human MTLE, featuring histological, electro-physiological, and pharmacological conditions of human pharmaco-resistant and non-convulsive MTLE.
It is therefore the most relevant predictive model for the qualification of Anti Seizure Medications (ASMs).
A Predictive Approach with Translational EEG Biomarkers
SynapCell’s MTLE model uses advanced EEG biomarkers to monitor non-convulsive seizures, mirroring human epilepsy. This innovative approach, developed through extensive R&D, offers drug discoverers crucial insights for assessing molecule efficacy at the preclinical stage, accelerating epilepsy treatment development.
SynapCell's MTLE Model is a Reference on the Market
Unique know-how in MTLE modeling makes SynapCell MTLE model the most robust and translational model for Focal Epilepsy on the market today.
SynapCell is partnering with a World recognized Epilepsy expert, approved by the NINDS ETSP Program.
“Drug-resistant epilepsies remain to this day a challenge, and there is a need for translational models to empower preclinical drug discovery. SynapCell’s MTLE mouse model is clinically relevant as it closely replicates the physiopathological, electrophysiological, and pharmacological features of human temporal lobe epilepsy. Having this model available in the ADD Program is a chance and a great asset for the ETSP.”
Pr. Karen S. Wilcox, Director of the ADD Program
From Small Molecules to Gene Therapies,
SynapCell Offers a Wide Range of Medication Assessments
Key Features
of the MTLE Model
The SynapCell MTLE model – and its associated HPD EEG biormarker – is recognized by the market as one of the most robust, relevant and translational models for evaluating compounds for Focal Epilepsy. SynapCell’s MTLE model is used by world-renowned epilepsy experts and approved by the NINDS ETSP program.
SynapCell’s MTLE non convulsive mouse model mirrors human pharmaco-resistant MTLE with the same histological, electro-physiological, and pharmacological conditions. This model is recognized as one of the most robust and translational model for Focal Epilepsy on the market today.
The MTLE mouse is a non-convulsive model of focal, pharmacoresistant epilepsies that perfectly mirrors human non-convulsive focal, pharmacoresistant MTLE epilepsy.
The MTLE mouse model is non-convulsive. Seizures are monitored within the brain assessed with appropriate EEG methods and EEG biomarkers (HPD).
After 3 weeks of epileptogenesis, MTLE mouse model shows the same epileptic disorders as human MTLE, non-convulsive and drug-resistant, making it the ideal model to test drug efficacy for focal epilepsy.
The MTLE mouse is a non-convulsive model of focal, pharmacoresistant epilepsies. Its EEG reveals spontaneous and recurrent Hippocampal Paroxysmal Discharges (HPD), which are used as objective EEG biomarkers to reliably evaluate the effect of antiseizure medications (ASMs) in vivo.
The SynapCell’s MTLE mouse model is validated by a pharmacology reference:
Voltage-gated channel:
– Valproate
– Carbamazepine
– Lamotrigine
– Retigabine
Gabaergic system:
– Diazepam
– Phenobarbital
– Vigabatrin
Others:
– Levetiracetam
– Pregabalin
Drug Discovery Assays
with the MTLE Model
Rapidly test a library of compounds to identify potential drug candidates.
Identify, optimize and test promising compounds in terms of efficacy and pharmacological properties to determine their potential as drug candidates.
Evaluate how biological systems react to varying drug concentrations. The resulting dose-response curve provides vital information on drug potency, efficacy, therapeutic range, and safety, guiding crucial decisions in drug development.
Epileptogenesis, by which a normal brain develops a tendency for recurrent seizures, is a key focus for developing new antiseizure medications that aim to prevent, modify, or reverse the progression of epilepsy, rather than just treating symptoms.
Assess the potential of your compound to modify epilepsy in a long term manner .
Gene therapy for focal epilepsy involves introducing genetic material into specific brain regions to modify neuronal excitability, potentially reducing seizures in drug-resistant cases. It’s an emerging approach in epilepsy drug discovery.
The MTLE model associated with its EEG biomarker can be used for a large range of assays for compound testing for Epilepsy… but not only! This model is also relevant to evaluate the potentiating or synergistic effects of an antiseizure medication when combined to other drugs and identify the most effective drug associations.
You can also combine a MTLE study (focal epilepsy) with a GAERS study (generalized epilepsy) to derisk your compounds, identify seizure-aggravating effects and more importantly, align your preclinical strategy with your clinical roadmap to validate your antiseizure medication (ASM).
POSTER
The SynapCell MTLE Model, a Predictive Model of Focal Epilepsy for Drug Discovery
Discover a powerful preclinical tool accelerating drug-resistant epilepsy research. This MTLE model accurately mirrors human focal epilepsy, capturing drug sensitivities and crucial EEG biomarkers. Revolutionize MTLE treatment strategies with this invaluable resource, offering researchers unparalleled insights to develop innovative therapies and advance epilepsy understanding.
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POSTER
Powered by Cue®, SynapCell's Predictive In Vivo EEG Platform
SynapCell’s MTLE model and its associated EEG biomarker (HPD) are processed on Cue® platform, our innovative translational in vivo EEG platform, designed to predict the in-human efficacy of your drug candidates at the preclinical step. Cue® is the results of decades of R&D, and combines SynapCell’s know-how, expertise and scientific excellence in terms of brain surgery, EEG signal recording and processing, and analysis.
Using Cue®, we transform preclinical data into actionable insights, offering end-to-end support for informed decision-making in CNS drug discovery.
THE SCIENCE CORNER
MTLE Hippocampal Sclerosis
Mesial Temporal Lobe Epilepsy involves seizures originating in the internal structures of the temporal lobe, in particular the hippocampus. MTLE epilepsy often results from sclerosis of the hippocampus. This hippocampal sclerosis is reproduced in SynapCell’s MTLE model.
Epileptogenesis
After 3 weeks of epileptogenesis, MTLE mouse model shows the same epileptic disorders as human MTLE, non-convulsive
and drug-resistant, making it the ideal model to test drug efficacy for focal epilepsy.
HPD, SynapCell's EEG Biomarker for the MTLE Model
Hippocampal Paroxysmal Discharges (HPDs) are EEG biomarkers of brain hyperexcitability observed in epilepsy. Characterized by bursts of high-frequency spikes and sharp waves, they typically last for several seconds. HPDs originate in the hippocampus, particularly the dentate gyrus, and propagate to other regions. They are considered non-convulsive focal seizures and are used to study epilepsy and test new therapies. HPDs provide valuable insights into epileptogenesis and serve as a tool for evaluating potential antiepileptic treatments in preclinical research.
Compare your Compound vs Standard of Care and Demonstrate Superior Effect
We have validated the model-biomarker duo (MTLE mouse – HPD) by a pharmacology of reference and demonstrated a differential sensitivity to ASMs with a greater efficacy of drugs that facilitate GABAergic transmission. This is what makes the model a powerful tool to identify new treatments for drug-resistant forms of focal epilepsies.
Let's Talk About Your Research Project!
More than a CRO, a team of collaborators – we are your neuroscience dream team specialized in preclinical EEG! We don’t just produce data; we’re your partners from concept to conclusion. We translate raw EEG data into meaningful and clinically relevant endpoints, delivering clear insights leading to data-based decisions. Choose SynapCell for cutting-edge science with an irresistible touch of fun!
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