Suppression of har-1/CHCHD10 phenotypes for ALS-FTD therapy discovery.

Mutations in CHCHD10 are linked to a variety of neurodegenerative diseases, including amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD). The Caenorhabditis elegans orthologue of CHCHD10 is har-1 , and we investigated whether har-1 mutants could be used for therapeutic discovery in ALS-FTD. Our results show that the small molecule pioglitazone and the probiotic Lacticaseibacillus rhamnosus HA-114 can alleviate har-1 mutant phenotypes. These findings suggest that har-1 mutants are suitable for modifier screens and could be adapted for high-throughput drug screening and microbiome studies to aid in discovering therapies for ALS-FTD.