Translational Advancement of Somatostatin Gene Delivery for Disease Modification and Cognitive Sparing in Intractable Epilepsy
Abstract
To test the safety and efficacy of somatostatin gene delivery as a potential therapeutic approach to epilepsy, an established rodent model is used in which electrical brain stimulation at current levels initially without effect gradually produce a persistent state where severe seizures occur reliably. Animals tested during the reporting period establish that somatostatin gene delivery after development of maximal seizure susceptibility can produce complete amelioration of a seizure-prone state. The therapeutic effect is essentially all or nothing. The responder rate is 30-40%, below the 70% observed when gene delivery preceded kindling, but comparable to extant antiepileptic medication. Responder and non-responder cohorts cannot be explained by variation in injection placement, transduction efficiency, electrographic seizure variables, effects on seizure-stimulated brain stem cell division or differentiation, or obvious brain pathology. Kindling increased new cell generation in hippocampus, and somatostatin gene expression reversed the effect of kindling.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2016
- Accession Number
- AD1035719
Entities
People
- Brandi K. Ormerod
- Michael A. King
- Paul R. Carney
Organizations
- University of Florida