EXCELLENCE
in preclinical seizure derisking
CNS Drug Safety
Collaborate with our seasoned drug safety experts to minimize clinical trial risks.
SCIENTIFIC
RIGOR
fast timelines
Assessing the seizure potential of an experimental drug
EEG is an established translatable method for exploring seizure risk of an investigational drug. Defining seizure risk requires a thorough examination of EEG, aligned with behavioral measures. EEG seizure risk biomarkers include detecting bona fide paroxysmal events (seizures) as well as prodromal events indicative of an increased risk of seizure.
We understand the nuanced effects that pharmaceutical compounds can have on EEG and provide safety interpretations guided by our robust knowledge of paroxysmal EEG and prodromal variants in multiple species.
Types of Seizures
The goal of a CNS safety study is to detect and characterize both convulsive and nonconvulsive seizure types, note their frequency, and identify postictal and interictal patterns. The findings are then integrated into the larger context of the program and can serve as translational information for clinicians.
NOAEL for Seizure Risk
If paroxysmal events are detected, the 'no observed adverse effect level' (NOAEL) of an experimental compound is set as the dose level that has not been associated with prodromal events or seizures.
Seizure Risk or Pharmacologic Effect?
In addition to its use as a biomarker of drug efficacy, quantitative EEG (qEEG) can be used preclinically and in clinical trials to distinguish between desirable pharmacological effects and potential seizure risks, thus helping to define a more precise No Observed Adverse Effect Level (NOAEL).
SLEEP-WAKE CYCLES
AND SEIZURE RISK
Sleep architecture analyses can be integrated with advanced monitoring technologies such as video-EEG telemetry to increase the sensitivity of preclinical CNS risk assessments.
Including EEG-derived sleep metrics in a preclinical safety study provides additonal insights into seizure mechanisms and aligns preictal (before seizure onset) and postictal (after seizure) states with specific changes in sleep-wake architecture.
Preictal changes may include alterations in sleep spindles, slow-wave activity, or arousal thresholds, indicating increased neuronal excitability and impending seizure onset. Postictal states may be characterized by changes in EEG background activity, sleep fragmentation, and alterations in sleep continuity, reflecting the physiological consequences of seizure activity on sleep.
SOURCE
LOCALIZATION
IN EPILEPSY
RESEARCH
PCEC’s brain mapping experts develop custom source localization software for translational medicine, surgery applications, and neuroscience research.
Understanding Epilepsy Mechanisms
An accurate estimation of epileptogenic regions is possible by noninvasive methods based on advanced quantitative EEG using source localization methods such as swLORETA.
Research using seizure foci localization techniques helps uncover the underlying mechanisms of epilepsy. By studying the brain activity associated with seizures, researchers gain insights into how epileptic networks function and how seizures propagate through the brain. This knowledge can contribute to the development of more effective treatments and interventions for epilepsy.
Epilepsy Biomarkers
Biomarkers are measurable indicators of biological processes or disease states. By correlating specific electrical neuroimaging patterns with seizure activity or biomolecular signatures, we help identify potential biomarkers for diagnosis, prognosis, and treatment response assessment in epilepsy patients.
Innovations in Countermeasure Research Methods
The efficacy of putative anticonvulsants against the severe CNS effects of nerve agents requires sensitive assessments of electrographic variants of seizures typically associated with the toxic exposure.
Our team has developed a standardized and sensitive method of status epilepticus severity assessment in rodents treated with organophosphates, based on combined behavioral and electrophysiological criteria.
