JR11 - Oral communication - Nour HALABI

Nour Halabi, a first-year PhD student in the Kabashi team, presents her research on FUS mutations in ALS using a zebrafish model. She begins by introducing FUS as a primary cause of juvenile ALS, characterized by skeletal muscle atrophy and FUS mislocalization. Previous work in her team established a zebrafish model replicating key ALS features, including reduced survival and locomotor defects. Her study focuses on two aims: characterizing metabolic and transcriptomic alterations and validating therapeutic strategies. She found structural abnormalities in skeletal muscle fibers and mitochondrial disorganization. RNA sequencing revealed downregulated metabolic pathways, and metabolomics confirmed decreased levels of free fatty acids, carnitine, and acetylcarnitine, suggesting impaired fatty acid beta-oxidation. The PPARalpha pathway was identified as a key downregulated pathway. Rescue experiments injecting a PPARalpha plasmid improved swimming behavior, and treatment with fenofibrate, a PPARalpha agonist, also enhanced locomotion and swimming patterns. These results suggest that targeting PPARalpha could be a promising therapeutic strategy for FUS-ALS. The talk concludes with a question about fenofibrate’s brain penetration, acknowledging limitations and the preliminary nature of the results.