Preclinical Evaluation of the Assembly Modulator PAV-615 in a Mouse Model of <i>C9orf72</i>-Associated ALS/FTD.

ABSTRACT: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are fatal neurodegenerative diseases that share clinical and pathological features, as well as genetic causes. A G₄C₂ repeat expansion in chromosome 9 open reading frame 72 (C9orf72) is the most common genetic cause of ALS and FTD, collectively referred to as c9ALS/FTD. Assembly modulation is a new therapeutic approach which appears to target allosteric sites on aberrant forms of multi-protein complexes and restore them to the healthy state. Recent findings demonstrate that tetrahydroisoquinolone (THIQ)-based protein assembly modulators can ameliorate ALS/FTD-associated phenotypes in cellular and animal models. In the present study, we investigated the effects of PAV-615, a novel and advanced

SUBMITTER: Su J 

PROVIDER: S-EPMC12732003 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature