Fenfluramine increases survival and reduces markers of neurodegeneration in a mouse model of Dravet syndrome.

ABSTRACT:

Objective

In patients with Dravet syndrome (DS), fenfluramine reduced convulsive seizure frequency and provided clinical benefit in nonseizure endpoints (e.g., executive function, survival). In zebrafish mutant scn1 DS models, chronic fenfluramine treatment preserved neuronal cytoarchitecture prior to seizure onset and prevented gliosis; here, we extend these findings to a mammalian model of DS (Scn1a^+/- mice) by evaluating the effects of fenfluramine on neuroinflammation (degenerated myelin, activated microglia) and survival.

Methods

Scn1a^+/- DS mice were treated subcutaneously once daily with fenfluramine (15 mg/kg) or vehicle from postnatal day (PND) 7 until 35-37. Sagittal brain sections were processed for immunohistochemistry using antibodies to de

SUBMITTER: Cha J 

PROVIDER: S-EPMC10839300 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature