The TRKB Agonist 7,8-dihydroxyflavone Alleviates DNA Damage and Apoptosis in a Neuronal Cell Model of Friedreich’s Ataxia

Galán-Cruz, J., Vicente-Acosta, A., Loría, F. et al. The TRKB Agonist 7,8-dihydroxyflavone Alleviates DNA Damage and Apoptosis in a Neuronal Cell Model of Friedreich’s Ataxia. Mol Neurobiol 63, 580 (2026). doi:10.1007/s12035-026-05856-2 

We found evidence of mitochondrial dysfunction concomitant with DNA damage and enhanced cell death due to FXN deficiency in cultured neurons. The treatment with 7,8-DHF was able to reduce the markers of genotoxicity and apoptosis, without restoring the impaired mitochondrial function nor the total cell death, possibly through ferroptosis, revealing a partial neuroprotective effect insufficient to halt the neurodegenerative process in this in vitro model of FRDA.

Novel Precision Gene Therapy for Friedreich’s Ataxia with Dr. Gabriel Brooks Solid Biosciences

Apr 23, 2026 . Solid Biosciences

 Dr. Gabriel Brooks is Chief Medical Officer at Solid Biosciences, a precision molecular genetic medicines company focused on rare cardiovascular and neuromuscular diseases, including Friedreich's ataxia. Currently, there are very limited treatments for this rare, progressive neurologic disease caused by a genetic deficiency. Solid Biowsciences' novel gene therapy uses dual-route administration to deliver directly to the heart and brain and to replace the missing frataxin gene, which is critical for energy production.

Nomlabofusp Treatment Produces Frataxin Levels That Correlate Across Peripheral Tissues: Preclinical and Clinical Support for Surrogate Tissue Sampling

De Toni F, Hamdani M, Patadia C, Shankar G. Nomlabofusp Treatment Produces Frataxin Levels That Correlate Across Peripheral Tissues: Preclinical and Clinical Support for Surrogate Tissue Sampling. Clin Transl Sci. 2026 May;19(5):e70565. doi: 10.1111/cts.70565. PMID: 42033121; PMCID: PMC13109711. 

This study evaluated whether nomlabofusp‐derived hFXN concentrations covary across accessible peripheral matrices and FRDA‐relevant tissues, supporting the feasibility of surrogate tissue sampling to monitor drug‐derived hFXN exposure.

Targeting exercise, energy, or both in Friedreich's ataxia

Schulz J, Reetz K., Targeting exercise, energy, or both in Friedreich's ataxia,  The Lancet Neurology, 25, 435-437, doi:10.1016/S1474-4422(26)00129-8

Friedreich's ataxia is a progressive, multisystem disorder causing neurological disability along with musculoskeletal, metabolic, and cardiac involvement.1 A consistent feature is markedly reduced cardiopulmonary fitness, which matters clinically because peak aerobic capacity correlates with functional limitations and might affect long-term health risks. To address impaired cardiopulmonary function, a phase-2, single-site, randomised, 2 × 2 factorial trial tested whether an individualised, remotely supervised, home exercise programme, the NAD+ precursor nicotinamide riboside, or a combination thereof could improve cardiopulmonary fitness over 12 weeks in children and adults with Friedreich's ataxia.

Safety and efficacy of individualised exercise and NAD+ precursor supplementation in patients with Friedreich's ataxia in the USA: a single-centre, 2 × 2 factorial, randomised controlled trial

Lin K, Bucha A, McSweeney K et al. Safety and efficacy of individualised exercise and NAD+ precursor supplementation in patients with Friedreich's ataxia in the USA: a single-centre, 2 × 2 factorial, randomised controlled trial The Lancet Neurology, 25, 469-481. doi:10.1016/S1474-4422(26)00082-7 

 Friedreich's ataxia is a rare, chronic, progressive, neurodegenerative condition affecting multiple organ systems, including neurological, musculoskeletal, cardiac, and endocrine systems, and is marked by low cardiopulmonary fitness. We tested the effect of exercise and NAD+ precursor supplementation with nicotinamide riboside, which have each shown benefits in animal and early clinical studies, on cardiopulmonary fitness in individuals with Friedreich's ataxia.

From Genetic Mutation to Therapy in Friedreich Ataxia: Molecular Mechanisms, Therapeutic Advances, and Translational Challenges

Osaki, Y.; Haque, U. S.; Yokota, T. From Genetic Mutation to Therapy in Friedreich Ataxia: Molecular Mechanisms, Therapeutic Advances, and Translational Challenges. Preprints 2026, 2026041108. doi: 10.20944/preprints202604.1108.v1 

This review provides a comprehensive overview of the evolving therapeutic landscape in FRDA, highlighting mechanistic rationales, preclinical progress, clinical trial outcomes, and the key translational challenges that must be addressed to achieve durable disease modification.

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.

Generation of Friedreich's ataxia induced pluripotent stem cells carrying the FXN c.165 + 5G>C splicing mutation

Yameogo P, Gerhart BJ, Sentmanat MF, Neilson A, Cui X, Verma M, Lynch DR, Napierala JS, Napierala M. Generation of Friedreich's ataxia induced pluripotent stem cells carrying the FXN c.165 + 5G>C splicing mutation. Stem Cell Res. 2026 Mar 16;93:103966. doi: 10.1016/j.scr.2026.103966. Epub ahead of print. PMID: 41865460. 

 Friedreich's ataxia (FRDA) is a multisystem, autosomal recessive disease caused by biallelic expansion of GAA repeats in intron 1 of the frataxin gene (FXN). While ∼96% of FRDA patients carry expanded GAA repeats on both FXN alleles, ∼4% are compound heterozygous with expanded GAA repeats on one allele and another mutation on the second allele. We generated induced pluripotent stem cells from blood lymphocytes from a FRDA patient carrying the FXN c.165 + 5G > C point mutation, which interferes with canonical splicing of intron 1 of the FXN gene. These cells allow for development of therapeutic approaches that target splicing defect in FRDA.