442 FRATAXIN IS DOWNREGULATED IN COLONIC INFLAMMATION DISRUPTING EPITHELIAL HOMEOSTASIS

Mo Wang, Xinqian Meng, Qiong Guo, Chunyan Peng, LEI WANG; 442 FRATAXIN IS DOWNREGULATED IN COLONIC INFLAMMATION DISRUPTING EPITHELIAL HOMEOSTASIS, Gastrointestinal Endoscopy, Volume 103, Issue 5, Supplement, 2026, Page S-882, ISSN 0016-5107, doi: 10.1016/S0016-5107(26)02275-3. 

This study identifies a novel link between frataxin (FXN) and ulcerative colitis (UC), demonstrating that its role extends beyond the nervous system and heart to intestinal health.

In Colonic Inflammation, FXN levels are drastically reduced in the colonic mucosa of patients with active UC, lower frataxin levels correlate directly with increased inflammatory severity.

Pathogenesis, FXN deficiency triggers mitochondrial energy failure and oxidative stress within the gut, compromising the epithelial barrier and inducing cell death. 

Conclusion: Frataxin is essential for colonic homeostasis. This suggests the FXN pathway as a potential therapeutic target for inflammatory bowel diseases and provides a mechanistic explanation for gastrointestinal complications in Friedreich’s Ataxia patients.

CGG, CAG, and GAA: Genome-wide comparison of the disease linked trinucleotide short tandem repeats

Annear DJ, Vandeweyer G, Kooy RF. CGG, CAG, and GAA: Genome-wide comparison of the disease linked trinucleotide short tandem repeats. BMC Genomics. 2026 Feb 18;27(1):302. doi: 10.1186/s12864-026-12651-9. PMID: 41709137; PMCID: PMC13020279. 

This paper offers a new genomic perspective on Friedreich's Ataxia by analyzing the behavior of the GAA triplet in comparison to other pathogenic repeats (such as Huntington's CAG).

This study highlights that Friedreich's Ataxia (FRDA) is unique due to the specific nature of the GAA repeat, setting it apart from other repeat-expansion diseases:

- Extreme Instability: GAA is the most abundant and polymorphic triplet in the human genome, explaining its intrinsic tendency for the pathological expansion found in the FXN gene. 

- Key Location: Unlike other repeats, GAA sequences are concentrated in introns, validating why FRDA results in gene silencing rather than direct protein alteration. 

FRDA is not merely a genetic error but a consequence of the evolutionary fragility of the GAA sequence, necessitating DNA-stabilization-specific therapeutic

Comprehensive Review of Anesthetic Strategies for Patients With Neurodegenerative Diseases

Grabarczyk Ł. Comprehensive Review of Anesthetic Strategies for Patients With Neurodegenerative Diseases. Med Sci Monit. 2026 Apr 11;32:e950453. doi: 10.12659/MSM.950453. PMID: 41964193; PMCID: PMC13081753.

This article aims to review the perioperative anesthetic management of patients with NDDs, including Huntington disease, (spino)cerebellar ataxia, Friedreich ataxia, Creutzfeldt-Jakob disease, and amyotrophic lateral sclerosis.

Friedreich Ataxia (Book)

Williams CT, Maheshwary A.; Friedreich Ataxia. 2026 Mar 22. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan–. PMID: 33085346. 

Friedreich ataxia (FRDA) represents the most common inherited form of ataxia, accounting for approximately 50% of all ataxia cases. Currently, the prevalence in the United States ranges from 1 in 30,000 to 50,000 individuals, with higher rates in Europe. First described in 1863 by the German clinician Nikolaus Friedreich...

Home-Based Telerehabilitation for Core Stability in Hereditary Ataxia: Feasibility and Preliminary Effects of a Pilot RCT

Masbernat-Almenara M, Peláez-Hervás S, Fernández-Lago H, Serra-Rusiñol L, Rubí-Carnacea F, Martínez-Navarro O, Tersa-Miralles C, Muñoz E, Rubinat-Arnaldo E, Cabanas-Valdés R. Home-Based Telerehabilitation for Core Stability in Hereditary Ataxia: Feasibility and Preliminary Effects of a Pilot RCT. NeuroRehabilitation. 2026 May;58(3):440-452. doi: 10.1177/10538135261431333. Epub 2026 Apr 8. PMID: 41949495. 

Core stability exercises (CSE) have shown efficacy in improving trunk function in individuals with hereditary ataxia (HA), but adherence to home programs is often low. Telerehabilitation (TR) could facilitate remote program delivery.

MuFaDDG: A Sequence-Based Multiscale Feature Fusion Framework for Protein Stability Changes Prediction

Gong J, Ma P, Ren Z, Li S, Fu Z, Sun P, Ni M, Bo X. MuFaDDG: A Sequence-Based Multiscale Feature Fusion Framework for Protein Stability Changes Prediction. Bioinformatics. 2026 Apr 29:btag196. doi: 10.1093/bioinformatics/btag196. Epub ahead of print. PMID: 42057285.  

The study introduces MuFaDDG, a sequence-based tool for predicting protein stability changes. Frataxin was used as the primary case study (via the CAGI5 challenge) to validate the model's performance. MuFaDDG achieved high accuracy (ACC: 0.81) in predicting how mutations affect frataxin's stability, outperforming existing state-of-the-art methods.Conclusion: The model proves highly effective at identifying destabilizing mutations in frataxin, which is critical for understanding diseases like Friedreich's Ataxia.

Integrative network pharmacology delineates dual GPCR and non-GPCR mechanisms of blended and individual Taikong Blue lavender and Pingyin rose essential oils in neurodegenerative and psychiatric disorders

Raka RN, Zhang Z, Xiao J, Wu H. Integrative network pharmacology delineates dual GPCR and non-GPCR mechanisms of blended and individual Taikong Blue lavender and Pingyin rose essential oils in neurodegenerative and psychiatric disorders. Comput Biol Med. 2026 May 15;208:111681. doi: 10.1016/j.compbiomed.2026.111681. Epub 2026 Apr 14. PMID: 41985299.  

The article explores the relationship with Friedreich's Ataxia through integrative network pharmacology. Friedreich's Ataxia is analyzed as one of the key neurodegenerative disorders sharing molecular pathways like oxidative stress and neuroinflammation. 

The study identifies specific compounds in essential oils that target proteins linked to the disease, suggesting a multi-target computational framework for potential neuroprotective treatments. It focuses on how these compounds interact with GPCR and non-GPCR targets to potentially modulate the biological dysfunctions seen in ataxia patients.

Listening in Spatialized Noise-Sentences (LiSN-S) as a Measure of Auditory Function in Friedreich Ataxia

Ali SAH, Early J, Farmer JM, Gelbard S, Corben L, Rance G, Lynch DR. Listening in Spatialized Noise-Sentences (LiSN-S) as a Measure of Auditory Function in Friedreich Ataxia. Cerebellum. 2026 Apr 24;25(3):60. doi: 10.1007/s12311-026-02000-7. PMID: 42029806; PMCID: PMC13109125. 

 LiSN -S testing captures audiologic dysfunction in FRDA in a manner that appears to dependent on genetic severity and to a lesser degree time.

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.”

Efficacy and Safety of Dimethyl Fumarate in Friedreich Ataxia: Primary Results From the Phase Two, Randomized, Double-blind, Placebo-controlled DMF-FA-201 Trial

S26 - Movement Disorders: Clinical Trials and Therapeutics. American Academy of Neurology. Francesco Sacca et al. 

DMF significantly increases transcription of the FXN gene, with long-term stability, to a degree that restores expression levels to those of healthy carriers. The drug appeared safe, with adverse events consistent with DMF pharmacovigilance.

Clinical Challenges in Managing Diabetes Mellitus in Friedreich’s Ataxia

Clinical Challenges in Managing Diabetes Mellitus in Friedreich’s Ataxia. Aarya Naik, Hooman Oktaei, Endocrine Practice , 32, S66-S67.   Doi:10.1016/j.eprac.2026.01.168 

In patients with FRDA, hyperglycemia generally develops at an average of 15 years after the onset of neurologic symptoms. Diabetes onset is often acute and ketosis-prone; appropriate management includes insulin at diagnosis. Past research has shown that often, the first presentation of diabetes in FRDA is ketoacidosis. In any given patient, diabetes may result from defects in insulin secretion by the pancreatic β-cells, impaired insulin action, or both. In FRDA, both insulin deficiency and insulin resistance have been reported.

Because metformin inhibits complex I of the mitochondrial respiratory chain, it should be used with caution. Exogenous insulin administration is often the best choice of treatment for FRDA patients. Regular screening for onset of diabetes as well as early initiation of insulin therapy should be part of overall management of FRDA.

Beyond the Diagnosis of Friedreich’s Ataxia: International Cultural Factors in Patient Decisions

Lauren Mitchell, Cara Stricklin, Nikola Dragojlovic, Beyond the Diagnosis of Friedreich’s Ataxia: International Cultural Factors in Patient Decisions, Archives of Physical Medicine and Rehabilitation, Volume 107, Issue 5, 2026, Page e42, ISSN 0003-9993, doi:10.1016/j.apmr.2026.02.108. 

To investigate the effectiveness of multiple interventions by an interdisciplinary team aimed at improving the functional level of a young woman with Friedreich's Ataxia (FA). Multiple interventions were trialed to include: neurolytic injections, high intensity gait training with various devices, various custom and prefabricated orthoses, neuromuscular re-education, a swallow study, expiratory muscular strength training, familial psychoeducation and community reintegration.

TLR4-mediated neuroimmune signalling drives proprioceptive neuron degeneration in Friedreich ataxia

TLR4-mediated neuroimmune signalling drives proprioceptive neuron degeneration in Friedreich ataxia, Deepika Mokkachamy Chellapandi, Peio Antoine-Uhart, Federica Pilotto, Helene Puccio. bioRxiv 2026.04.28.721289; doi:10.64898/2026.04.28.721289. 

 We identify Toll-like receptor 4 (TLR4) signaling as a key link between neuronal dysfunction and inflammatory response. Inhibition of TLR4 reduces cellular stress, restores neuronal integrity, and delays disease progression in vivo. These findings redefine FA as a disorder involving neuroimmune crosstalk and highlight TLR4 signaling as a potential therapeutic target.