Translational Advancement of Somatostatin Gene Delivery for Disease Modification and Cognitive Sparing in Intractable Epilepsy
Abstract
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 nonresponder 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, with a bias toward non-neuronal phenotypes, and somatostatin gene delivery uniformly suppressed this regardless of therapeutic efficacy against seizures.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2015
- Accession Number
- AD1002317
Entities
People
- Brandi K. Ormerod
- Michael A. King
- Paul R. Carney
Organizations
- University of Florida