Hypomagnetic Field Exposure Alters Iron-Sulfur Homeostasis and Oxidative Balance in a Frataxin-Deficient Insect System

Kang HM, Li B, Yan S, Zhang LL, Wan GJ, Zhang JZ, Pan WD. Hypomagnetic Field Exposure Alters Iron-Sulfur Homeostasis and Oxidative Balance in a Frataxin-Deficient Insect System. Insects. 2026 Apr 1;17(4):373. doi: 10.3390/insects17040373. PMID: 42042415; PMCID: PMC13116274. 

 HMF elevated reactive oxygen species (ROS) in frataxin-deficient brains. Transcriptomic analysis identified 202 differentially expressed genes under HMF in frataxin-silenced flies, including key regulators of iron metabolism and oxidative stress pathways. These findings demonstrate that HMF disrupts tissue-specific iron and sulfur homeostasis and intensifies oxidative stress in a frataxin-deficient insect system, underscoring its role as an environmental factor capable of aggravating metabolic fragility.

Astrocytic frataxin deficiency drives neurocognitive impairment in sickle cell mice

Novelli EM, Lenhart SC, Foley LM, Sekar N, Mondal P, Wang H, Hitchens TK, Ghosh S, Chan SY, Hu X, Hazra R. Astrocytic frataxin deficiency drives neurocognitive impairment in sickle cell mice. PNAS Nexus. 2026 Apr 8;5(4):pgag106. doi: 10.1093/pnasnexus/pgag106. PMID: 42037666; PMCID: PMC13108596. 

 Herein, we report that sickle cell mice (SS) have reduced expression of frataxin (FXN), a mitochondrial protein, in their astrocytes compared with normal control (AA) mice. A newly generated sickle bone marrow chimeric mouse with astrocyte-specific deletion of FXN (SSFXN-KO) showed worsening white-matter neuroaxonal damage compared with the normal mice lacking astrocytic FXN (AAFXN-KO) as well as with the SS mice with wild-type FXN expression (SSFXN-WT). The SSFXN-KO mice exhibited impaired cognitive function assessed by the functional novel object recognition (NOR) tests. Induction of FXN improved cognitive responses in the SS mice. Overall, our data demonstrate that astrocytic FXN plays a pivotal role in regulating neuroaxonal health and cognitive function in SCD.

BRD4 recruitment desilences transcription without erasure or depletion of repressive chromatin

BRD4 recruitment desilences transcription without erasure or depletion of repressive chromatin. Christopher J. Brandon, Sarah Robinson-Thiewes, Mangesh Kaulage, Wojciech Rosikiewicz, Matthew J. Cuneo, Joseph Brett, Jindpreet Kandola, Walter H. Lang, Jonathan Low, Ashraf Mohammed, Adithi Danda, Sam Rider, Marcus Valentine, Jason Ochoada, Brandon Young, Theresa Nguyen, Sandra J. Kietlinska, Aaron B. Taylor, Burkhard Hoeckendorf, Patrick Rodrigues, Wenwei Lin, Khaled Khairy, Beisi Xu, Anang A. Shelat, Taosheng Chen, Tanja Mittag, Aseem Z. Ansari bioRxiv 2026.04.10.717856; doi:10.64898/2026.04.10.717856

We find that BRD4 readily partitions into phase separated HP1 condensates in vitro and into HP1 puncta in patient-derived cells, thus presenting a mechanistic explanation for desilencing transcription without the dispersal of mesoscale repressive chromatin. Epigenetic drugs that gate sequential steps in transcription, synergistically stimulate FXN expression while concomitantly increasing, rather than eliminating, repressive H3K9me3 and HP1 levels. More broadly, this study highlights the dynamic nature of repressive chromatin and the context-dependence of epigenetic marks in regulating gene expression.

Modeling Friedreich’s ataxia with Bergmann glia-enriched human cerebellar organoids

Ryu, S., Inman, J., Hong, H. et al. Modeling Friedreich’s ataxia with Bergmann glia-enriched human cerebellar organoids. Commun Biol (2026). doi:10.1038/s42003-026-10180-5 

Furthermore, by generating hCBOs from patients with Friedreich’s ataxia (FRDA), we reveal disease-specific phenotypes that can be reversed by histone deacetylase (HDAC) inhibitors and gene editing by CRISPR-Cas9. Taken together, our advanced hCBO model provides new opportunities to investigate the mechanisms of cerebellar ontogenesis and utilize patient-derived iPSCs for translational research.

Glial-specific mitochondrial failure and redox imbalance drive regional vulnerability in Friedreich ataxia

Glial-specific mitochondrial failure and redox imbalance drive regional vulnerability in Friedreich ataxia. Arabela Sanz-Alcazar, Marta Portillo-Carrasquer, Israel Manjarres-Raza, Maria Pazos-Gil, Fabien Delaspre, Jordi Tamarit, Juan P. Bolanos, Joaquim Ros, Elisa Cabiscol; bioRxiv 2026.05.01.722124; doi:10.64898/2026.05.01.722124 

 These results highlight the vulnerability of sensory neurons and their supporting satellite glial cells. In contrast, in the cerebrum and cerebellum, astrocytes displayed earlier and more severe alterations than neurons, including impaired respiratory chain efficiency, disrupted complex I-III supercomplex interaction, elevated ROS, and hallmarks of ferroptosis. Neuronal abnormalities emerged later, suggesting that glial dysfunction precedes -or drives- neuronal pathology within the central nervous system. Overall, these findings reveal pronounced region and cell-type-specific vulnerabilities in FA and support the importance of targeting glial mechanisms -particularly iron dysregulation, oxidative stress, and ferroptosis- as targets for potential therapeutic strategies.

Voyager Reports First Quarter 2026 Financial and Operating Results

LEXINGTON, Mass., May 07, 2026 (GLOBE NEWSWIRE) -- Voyager Therapeutics, Inc Neurocrine partnership update: Neurocrine completed GLP toxicology with NBIB-‘223 for Friedreich’s ataxia (FA) and received FDA orphan drug designation. Neurocrine has stated that it intends to initiate a clinical trial with NBIB-‘223 in H2 2026, pending successful FDA IND clearance.

Solid Biosciences Testing Dual Delivery Gene Therapy in First-in-Human Friedreich's Ataxia Trial

Precision Medicine Online. Apr 16, 2026. NEW YORK – Solid Biosciences is advancing its first-in-human trial of SGT-212, an experimental gene therapy for the rare neuromuscular disorder Friedreich's ataxia. 

The dual route of administration is intriguing to Kisanuki, since Friedreich's ataxia implicates multiple tissues in the body. "If we used just systemic delivery, we might not fully benefit the neuro phenotype," he said. "But if we just focus on brain delivery, we're ignoring the cardiac phenotype."

Exploring US patient and caregiver perspectives on burden associated with Friedreich Ataxia

Lawson, R., Natarajan, S., Correll, J.R. et al. Exploring US patient and caregiver perspectives on burden associated with Friedreich Ataxia. J Patient Rep Outcomes (2026). doi:10.1186/s41687-026-01067-4  

Friedreich ataxia (FA) is a hereditary degenerative disease with clinical manifestations in multiple organs characterized by progressive gait and limb ataxia. Qualitative interviews were conducted with patients and caregivers to characterize the burden experienced related to FA symptoms and impacts.

PO-04-187 OVERACTIVITY OF MONOAMINE OXIDASE A IN A MOUSE MODEL OF FRIEDREICH’S ATAXIA CONTRIBUTES TO CATECHOLAMINERGIC ARRHYTHMIAS AND OXIDATIVE STRESS

Figueroa F, Bahriz S, Sellers R ... PO-04-187 OVERACTIVITY OF MONOAMINE OXIDASE A IN A MOUSE MODEL OF FRIEDREICH’S ATAXIA CONTRIBUTES TO CATECHOLAMINERGIC ARRHYTHMIAS AND OXIDATIVE STRESS Heart Rhythm, 23S711. doi:10.1016/j.hrthm.2026.03.1185 

 These findings identify impaired SR-localized β1AR signaling as a novel mechanism driving catecholaminergic arrhythmias in FA. Combined targeting of MAO-A and Nrf2 yields complementary benefits: clorgyline improving autonomic balance and OMAV enhancing redox defense, thereby restoring cardiac conduction and contractile function in FA hearts.

Dimethyl Fumarate Normalizes Expression of Friedreich Ataxia Gene

Neurology Today - American Academy of Neurology; APRIL 20, 2026,  Dan Hurley. 

Dr. Gramaglia said some patients already on omaveloxolone might be interested in combining it with DF. But “we don’t know if DMF as an add-on therapy with omaveloxolone would result in clinical improvements over either one individually,” she added. “We need to study it.”