ETSP Current Models and Workflow

The Epilepsy Therapy Screening Program (ETSP) evaluates investigational therapeutics using a range of models and assays, including new approach methodologies (NAMs) such as human induced pluripotent stem cells (iPSCs)-derived neurons and astrocytes and in vitro slice preparations, as outlined in the diagram and described below.

Identification Phase

1. Acute Seizure Models
   1. 6 Hz Electrical Stimulation Test
   2. Maximal Electroshock Test
   3. Time to Peak Effect, Effective dose, Tolerability Dose
2. Behavioral Tolerability Screens
   1. Rotarod Test
   2. Minimal Motor Impairment Test
   3. Locomotor Activity Test
   4. Modified Irwin Test
3. New Approach Methodologies (NAMs) and In Vitro Models
   1. Co-culture of human iPSC-derived neurons and astrocytes
   2. Spontaneous Bursting Slice from Post-Kainic Status Epilepticus Model
4. Chronic Seizure Models
   1. Corneal Kindling Seizure Test

Differentiation Phase

5. Acute Dosing
   1. Intra-Hippocampal Kainate Model
   2. Lamotrigine-Resistant Amygdala Kindling Model
6. 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
7. Indication-Specific Epilepsy Models
   1. Benzodiazepine Resistant Li-Pilocarpine Status Epilepticus Model
   2. Theiler’s Murine Encephalomyelitis Virus Model
   3. Dravet Syndrome Model
   4. Pentylenetetrazol-Induced Seizure Model

Disease Prevention and Modification

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

Pharmacokinetic (PK) Analysis

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