Reduction of interleukin-6 levels in patients with Friedreich's Ataxia treated with omaveloxolone

Di Stefano V, Lima S, Campo S ... Reduction of interleukin-6 levels in patients with Friedreich's Ataxia treated with omaveloxolone; Journal of the Neurological Sciences, 2026; 491. DOI:10.1016/j.jns.2026.126204 

 Omav confirmed a favorable safety and tolerability profile in adult patients with FRDA in a real-world setting after 48 weeks of treatment. The sustained reduction in IL-6 levels further supports a potential direct immunomodulatory effect of the drug, consistent with its proposed disease-modifying activity. However, further long-term studies are warranted to better define the efficacy of Omav in FRDA.

Autonomic neurons are intrinsically hyperexcitable in a Friedreich ataxia iPSC model

Autonomic neurons are intrinsically hyperexcitable in a Friedreich ataxia iPSC model; Shiang L (Max), Jarmon Lees, Haoxiang Zhang, Li Li, Mirella Dottori, Alice Pebay, Louise Corben, Martin Delatycki, Stephen Wilcox, Jeffrey Pullin, Jarny Choi, Davis McCarthy, Jill Napierala, Marek Napierala. bioRxiv 2026.10.06.757136; doi:10.64898/2026.10.06.757136 

 Bulk RNA sequencing of all three isogenic pairs revealed loss of extracellular matrix programs and activation of stress response pathways. The top differentially expressed gene was MEG3, a maternally imprinted long noncoding RNA, which was consistently upregulated across all three isogenic pairs. MEG3 sits within the imprinted 14q32 DLK1-DIO3 locus, whose maternally expressed noncoding transcripts were co-ordinately de-repressed in FRDA autonomic neurons. Competitive gene-set testing of 43 imprinted genes across 20 domains showed this to be specific to 14q32: no other imprinted domain was co-ordinately altered. Together, these findings establish hyperexcitability of autonomic neurons as a cell autonomous consequence of frataxin deficiency, accompanied by mitochondrial dysfunction. This provides a cellular basis for the increased sympathetic tone observed in clinical studies.

Exploring the molecular landscape of Friedreich ataxia with long-read sequencing

Sebastien Audet, Marjorie Labrecque, Valerie Triassi, Carolane Charest, Adrien Rihoux, Laura Hamilton, Grace Yoon, Antoine Duquette, Martine Tetreault, 1.45P Exploring the molecular landscape of Friedreich ataxia with long-read sequencing, Neuromuscular Disorders, Volume 67, Supplement 1, 2026, 106600, ISSN 0960-8966, doi:10.1016/j.nmd.2026.106600. 

 Data integration utilized custom bioinformatics pipeline. Following the analysis, we observe 1) a repeat length quantification that broadly correlates clinical data but exhibiting events of somatic expansion and non-homogeneous repeat motifs. 2) We identify regions of differential methylation near promoters that correspond to 3) genes exhibiting significant changes in expression. We 4) evaluated LRS-enabled alternative splicing/poly-A tailing detection and 5) assessed if the levels of differential methylation/expression correlate to increased repeat length. This project should consolidate the potential of LRS in clinical genetics and functional studies. Regarding FRDA, results should provide new insights into pathogenic mechanisms and potentially identify molecular signatures of the disease, assisting in the search for new therapeutic targets.