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.