AMT-260 Gene Therapy Study in Adults With Unilateral Refractory Mesial Temporal Lobe Epilepsy

Inclusion Criteria:

• Diagnosis of unilateral refractory MTLE

• History of seizures with an average of ≥ 2 documented focal impaired awarenessseizures or focal to bilateral tonic-clonic seizures per 30-day period in the 3months prior to screening.

• On a stable type and dose regimen of up to a maximum of 4 approved Anti SeizureDrugs for at least 6 months prior to screening.

• Confirmed unilateral hippocampal pathology and concordant unilateral seizure focus

• No evidence of focal neurocognitive dysfunction, inconsistent with diseasepathology- related MRI and/or (18F)FDG-PET findings.

• Women of childbearing potential (WOCBP) and fertile male subjects must be willingand able to use highly effective methods of birth control consistently and correctlythroughout the study.

• For WOCBP only: Negative pregnancy test.

Exclusion Criteria:

• Implanted devices that would contraindicate MRI; MRI-compatible devices must beimplanted ≥3 months prior to Screening (vagus nerve stimulation devices will be upto discretion of the Investigator).

• Any other contraindications for generalized anesthesia or surgery.

• Medications that could confound clinical (e.g., antipsychotic medication andanti-viral therapy) and laboratory evaluations or could affect a participant'ssafety or their ability to undergo the neurosurgical procedure or comply with theprocedures and study visit schedule.

• Any seizures with contralateral or extra-temporal icta onset captured on EEG.

• Dementia or other progressive neurological disorders and progressive brain lesions.

• Previous major disease-unrelated neurosurgical intervention due to intracranialtumor, trauma, or bleeding and/or history of previous intracranial surgery fortreatment of epileptic seizures, not including diagnostic stereo-EEG.

• Magnetic resonance imaging evidence of epileptogenic, extra-temporal lesions, ordual temporal lobe pathology.

• Inadequate vaccination status (including flu shots and other relevant immunizationssuch as COVID-19 per local guidelines and regulations).