ETSP Current Models and Workflow

Identification Phase

1. Acute Seizure Assays
   1. 6 Hz Electrical Stimulation in vivo seizure assay
   2. Maximal Electroshock in vivo seizure assay
   3. Time to Peak Effect, Effective dose, Tolerability Dose
2. Behavioral Tolerability Assessment
   1. Rotarod Test
   2. Minimal Motor Impairment
   3. Locomotor Activity
   4. Modified Irwin Test
3. Chronic Seizure Assays
   1. Kindling Seizure Test
   2. Spontaneous Bursting Slice Obtained In Vivo Post-Kainic Status Epilepticus

Differentiation Phase

4. Acute Dosing
   1. Intra-Hippocampal Kainate Model
   2. Lamotrigine-Resistant Amygdala Kindling Model
5. Subchronic Dosing
   1. Intra-Amygdala Kainate Model
   2. Post-Kainic Acid Status Epilepticus-Induced Spontaneous Recurrent Seizures Model – Phase I
   3. Post-Kainic Acid Status Epilepticus-Induced Spontaneous Recurrent Seizures Model – Phase II
6. Ancillary Drug Resistant Epilepsy Models
   1. Benzodiazepine Resistant Lithium-Pilocarpine Status Epilepticus Model
   2. Theiler’s Murine Encephalomyelitis Virus Model
   3. Dravet Syndrome Model
   4. Pentylenetetrazol Seizure Threshold Assay
   5. Co-cultured Human Induced Pluripotent Stem Cells (hiPSCs) assay using Multielectrode Array (MEA) platform

Pharmacokinetic (PK) Analysis

1. 1. Bioanalytical Method Development
   2. PK Analysis Associated with Activity Testing
   3. PK Analysis in Non-disease Models

Disease Prevention and Modification

1. 1. What is Disease Prevention and Modification?
   2. Post-Kainic Acid Status Epilepticus-Induced Spontaneous Recurrent Seizures
   3. Intra-Amygdala Kainate Model