Dynorphin-based "release on demand" gene therapy for drug-resistant temporal lobe epilepsy.

ABSTRACT: Focal epilepsy represents one of the most common chronic CNS diseases. The high incidence of drug resistance, devastating comorbidities, and insufficient responsiveness to surgery pose unmet medical challenges. In the quest of novel, disease-modifying treatment strategies of neuropeptides represent promising candidates. Here, we provide the "proof of concept" that gene therapy by adeno-associated virus (AAV) vector transduction of preprodynorphin into the epileptogenic focus of well-accepted mouse and rat models for temporal lobe epilepsy leads to suppression of seizures over months. The debilitating long-term decline of spatial learning and memory is prevented. In human hippocampal slices obtained from epilepsy surgery, dynorphins suppressed seizure-like activity, suggestive of a high pot

SUBMITTER: Agostinho AS 

PROVIDER: S-EPMC6783645 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature