Consulting and advising for preclinical epilepsy and neurological disease drug discovery

Dentatorubral-pallidoluysian atrophy (DRPLA) is a fatal neurodegenerative disease caused by a CAG repeat expansion in the atrophin-1 (ATN1) gene and is thought to arise from toxic gain-of-function mechanisms. This study evaluated the disease modifying impact of a novel antisense oligonucleotide (ASO) in a mouse DRPLA model.

ENX‑101 targets specific GABA receptor types (α2, α3, and α5 subunits) linked to seizure control, avoiding the α1 subtype responsible for strong sedation. This study reports the in vitro and in vivo studies to profile ENX-101, including activity in amygdala-kindled rats and the mouse 6 Hz test.

In preclinical epilepsy therapy screening, it is difficult to know which animal models can be most predictive of clinical success. This study establishes a framework to demonstrate that the models with the highest clinical concordance were: maximal electroshock test and 6 Hz test, followed closely by the corneal kindled mouse.