Longitudinal analysis shows GAA1 length and baseline clinical status as robust predictors of progression in Friedreich ataxia

Manrique L, Martínez-Dubarbie F, Pelayo-Negro AL, Benitez-Calle N, Sanchez-Pelaez MV, Cota-Gonzalez D, Loza R, Martinez-Díaz R, Irure-Ventura J, Sanchez-Quintana C, Sanchez I, Matilla-Dueñas A, Infante J. Longitudinal analysis shows GAA1 length and baseline clinical status as robust predictors of progression in Friedreich ataxia. J Neurol. 2026 Apr 9;273(5):259. doi: 10.1007/s00415-026-13812-2. PMID: 41954755; PMCID: PMC13065527.

Frataxin levels were significantly reduced in patients and correlated with GAA1 length and baseline severity. SARA, FARS–ADL, and INAS worsened significantly over time, while SCAFI and CCFS remained stable. GAA1 length and baseline SARA score emerged as the strongest predictors of progression. CSF NfL was elevated in younger patients and declined with age but did not correlate with severity or progression. These results support GAA1 length and baseline clinical status as robust predictors of progression and suggest limited utility of CSF NfL as a longitudinal biomarker particularly in later disease stages.

Hypomagnetic Fields Influence the Developmental Duration, Fecundity and Temperature Stress Resistance of Drosophila melanogaster via Frataxin-Associated Traits

Kang H, Wan G, Zhang J, Pan W. Hypomagnetic Fields Influence the Developmental Duration, Fecundity and Temperature Stress Resistance of Drosophila melanogaster via Frataxin-Associated Traits. Biology (Basel). 2026 Feb 27;15(5):391. doi: 10.3390/biology15050391. PMID: 41823819; PMCID: PMC12985338. 

 The impact of HMF on temperature stress resistance was particularly specific: it enhanced recovery from chill coma in control (GFP-RNAi) flies, while it accelerated recovery from heat shock in frataxin-silenced (fh-RNAi) flies. The mechanisms through which HMF modulate frataxin-associated phenotypes at a fundamental physical level warrant further investigation.

Arctigenin derivative (ARC-18) improved mitochondrial dysfunction and ameliorated frataxin deficiency symptoms via PGC-1α signaling

Gong Q, Han X, Liu T, Xiong B, Zhang B, Xie Y, Wan H, Ali T, Yang X, Li S. Arctigenin derivative (ARC-18) improved mitochondrial dysfunction and ameliorated frataxin deficiency symptoms via PGC-1α signaling. Genes Dis. 2025 Sep 1;13(4):101838. doi: 10.1016/j.gendis.2025.101838. PMID: 41884717; PMCID: PMC13011025.

Notably, co-treatment with the PGC-1α inhibitor SR-18292 abolished ARC-18 effects, confirming its dependence on PGC-1α activation to rescue mitochondrial deficits in FXN-deficient cells.