ESSENTIAL TREMOR
A Common Disorder, Yet Difficult to Treat
Essential Tremor (ET) represents the most prevalent neurological disorder, with a prevalence rate of 1.33%. Despite its commonality, the pathophysiology of essential tremor remains incompletely understood, and current therapeutic interventions demonstrate limited efficacy. The etiology of the disease is not fully elucidated, with approximately 50% of cases presenting as familial and the remaining 50% as sporadic.
Present treatments, such as propranolol, are capable of reducing tremor amplitude by up to 50% but exhibit efficacy in only approximately 40% of patients. Additionally, some potentially effective pharmacological agents have been associated with intolerable adverse effects. Fortunately, a range of drug candidates with diverse mechanisms of action are undergoing various stages of clinical trials. These include T-type calcium channel blockers, GABA A receptor positive allosteric modulators, and GABA-A Receptor Positive Allosteric Modulators.
There is a critical need to enhance outcome measures through the establishment of standardized methods for assessing tremor severity, thereby facilitating the evaluation of treatment efficacy.
SynapCell's EEG Biomarker: Beyond Tremors
Our harmaline rat model and its related EEG biomarker (ET band) represent a robust tool to empower decision-making processes in drug discovery for Essential Tremor. Harmaline induces tremor in rats and mice that develops within minutes and lasts up to several hours. This EEG assay provides a meaningful addition to behavioral studies, by evaluating the impact of treatments on the Essential Tremor EEG biomarker within the cerebellum and motor cortex.
A Translational Model for the Disease
- Harmaline has been demonstrated to induce tremors with a frequency range similar to that observed in humans with essential tremor (ET)..
- The cerebellum plays a crucial role in both ET and the Harmaline model.
- Neural oscillations in the thalamus and EEG correlate with behavioral tremor
Objective EEG Biomarker
The ET band EEG Biomarker helps quantify the intensity of effect of a compound in real time while remaining objective.
This enhance behavioral studies by evaluating the efficacy of the compound beyond clinical symptoms.
Pharmacological Profile Similar to Human Essential Tremor
Most drug proven to mitigate harmaline-induced tremor in animal models also exhibit a therapeutic benefits in patients with ET.
Propranolol, Carbamazepine and Ethanol have demonstrated efficacy in both humans and animals with ET, validating it as a predictive model.
Key Features
of the Harmaline Model
The harmaline model and essential tremor (ET) involve the same brain structures, with tremors occurring within a similar frequency range as observed in ET patients.
Compare the EEG power in the ET band to the behavioral tremor score, integrating both neurophysiological and behavioral data.
The ET band induced by Harmaline is reversed by known therapeutic agents such as propranolol, ethanol, and carbamazepine, demonstrating its predictive reliability for assessing potential treatments for ET.
Drug Discovery Assays
with the Harmaline Model
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.
Study how drugs interact with and affect the body, and examine the biological and physiological effects of drugs, their mechanisms of action, and the relationship between drug concentration and therapeutic response.
Develop additional treatments to enhance the efficacy of existing drugs. These therapies are designed to be used in combination with the main treatments, targeting different aspects of a disease or addressing the limitations of the main treatment to improve overall condition.
Several antiseizure medications such as primidone and carbamazepine demonstrated an effect against Essential Tremor.
POSTER
Translational Pharmacology in Essential Tremor: Relevance of Electrophysiological Biomarkers
In this poster, we characterize the effects of compounds with various mechanisms of action in the rat model of Essential Tremor. SynapCell’s biomarker/model duo provides a robust screening platform for identifying novel compounds targeting essential tremor. The Harmaline model exhibits strong predictive power by accurately replicating the pharmacological response observed in humans.
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POSTER
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APPLICATION NOTE
POSTER
EEG Biomarkers to Challenge Essential Tremor
Present treatments, such as propranolol, are capable of reducing tremor amplitude by up to 50% but exhibit efficacy in only approximately 40% of patients. Additionally, some potentially effective pharmacological agents have been associated with intolerable adverse effects. There is a critical need to enhance outcome measures through the establishment of standardized methods for assessing tremor severity, thereby facilitating the evaluation of treatment efficacy.
Powered by Cue®, SynapCell's Predictive In Vivo EEG Platform
SynapCell’s Harmaline rat model and its associated EEG biomarker (ET band) are processed on Cue®, our innovative translational in vivo EEG platform, which is designed to predict the in-human efficacy of your drug candidates during the preclinical step. Cue® is the result of decades of R&D, combining SynapCell’s know-how, expertise and scientific excellence in the fields of brain surgery and EEG signal recording, 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
Diagrammes à mettre à jour
A Pharmaco-induced Model
Acute administration of Harmaline at 15mg/kg leads to stable and oscillatory activites in the 30-55Hz Frequency band, called ET band, in the primary motor cortex and the cerebellum. The effect persists for several hours.
Behavioral Endpoint: The Tremor Scale
Acute administration of harmaline lead to significant tremor increase, yet no effect of propranolol on motor components was observed.
ET Band, SynapCell's EEG Biomarker for the Harmaline Model
The ET Band and harmaline mouse model shows the dose-response effect of drugs such as propranolol. Here, propranolol dose-dependently reduced harmaline-induced EEG biomarker in rats.
Despite the lack of observed effect of propranolol on motor components, a pharmacological effect could be very well seen in the ET Band.
Both endpoints bring powerful data, and allow drug developers to assess the effect of their compound on both tremors and cortical activity.
References: https://www.mdpi.com/2218-273X/11/12/1813
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