A case of Friedreich Ataxia and left ventricular hypertrophy induced by FXN gene mutation

Zhou BY, Ren N, Zhang YY, Geng J. [A case of Friedreich Ataxia and left ventricular hypertrophy induced by FXN gene mutation]. Zhonghua Xin Xue Guan Bing Za Zhi. 2025 Nov 24;53(11):1271-1274. Chinese. doi: 10.3760/cma.j.cn112148-20250917-00659. PMID: 41287297.

 弗里德赖希共济失调（FRDA）是欧洲常见的常染色体隐性遗传疾病，但在中国较为罕见，目前国内尚无经基因诊断的FRDA病例报道。该文报道1例运动发育迟缓且步态不稳的男性患者，超声心动图检测到左心室肥厚，心脏磁共振成像显示左心室壁心肌多灶性钆对比剂延迟强化。基因检测显示FXN基因复合杂合突变：c.482+2T>A突变和第一内含子GAA三核苷酸序列异常扩增（8次和>66次重复），其中GAA拷贝数大于66次达到FRDA的致病性扩增阈值。. 

Friedreich ataxia (FRDA) is a common autosomal recessive disease in Europe, but it is rarer in China, and no genetically diagnosed FRDA cases have been reported in China. This article reported a male patient with delayed motor development and unstable gait, left ventricular hypertrophy was detected by echocardiography, and cardiac magnetic resonance imaging showed delayed enhancement of myocardial multifocal gadolinium contrast agent in the left ventricular wall. Genetic testing revealed complex heterozygous mutations in the FXN gene: c.482+2 T>A mutation and abnormal amplification of the first intron GAA trinucleotide sequence (8 and >66 replicates), where the GAA copy number was greater than 66 to reach the pathogenic amplification threshold of the FRDA.

Survival in Brazilian Patients with Friedreich´s Ataxia

Machado DS, Silveira C, Vinagre AM, Rezende TJR, Dogini D, Martinez ARM, França MJC. Survival in Brazilian Patients with Friedreich´s Ataxia. Cerebellum. 2025 Nov 22;24(6):182. doi: 10.1007/s12311-025-01936-6. PMID: 41273607.

Shorter life expectancy was found: in men relative to women (Mean age: 54.0 yo vs. 56.8 yo, p = 0.03), in patients with classical relative to late-onset (Mean age: 52.2 yo vs. 71.0 yo, p < 0.01) and in patients with cardiomyopathy relative to those without it (Mean age: 50.8 yo vs. 65.0 yo, p < 0.01). FRDA impacts life expectancy and death is primarily from cardiac and pulmonary causes. Male sex, early onset and presence of cardiomyopathy are negative survival prognostic markers.

NFS1, together with FXN, protects cells from ferroptosis and DNA damage in diffuse large B-cell lymphoma

Shi X, Zhao Y, Gao HY, Yang W, Liao J, Wang HH, Wang XT, Yan W. NFS1, together with FXN, protects cells from ferroptosis and DNA damage in diffuse large B-cell lymphoma. Redox Biol. 2025 Nov;87:103878. doi: 10.1016/j.redox.2025.103878. Epub 2025 Sep 23. PMID: 41005206; PMCID: PMC12505007.

We demonstrated that ISC-related proteins NFS1 and FXN protect DLBCL cells from ferroptosis and DNA damage, thus exhibiting an essential role in DLBCL progression.

Partial Bypass of Frataxin Deficiency by ISCU M141I Restores Cytosolic and Nuclear Fe-S Cluster Assembly

Mosbach V, Maio N, Diedhiou N, Hennick A, Dall'Agnol L, Reutenauer L, Marczak L, Birling MC, Eisenmann A, Martelli A, Hélène PH. Partial Bypass of Frataxin Deficiency by ISCU M141I Restores Cytosolic and Nuclear Fe-S Cluster Assembly. bioRxiv [Preprint]. 2025 Sep 6:2025.09.03.673074. doi: 10.1101/2025.09.03.673074. PMID: 41019637; PMCID: PMC12466782. 

 Altogether, our results reveal a previously unrecognized compartment-specific rescue of Fe-S cluster dependent processes by the ISCU M141I variant in mammalian cells, raising for the first time the possibility of compartmental regulation of Fe-S cluster biogenesis.

Scoliosis Surgery in a Patient With Advanced Friedreich's Ataxia-It Is Not Too Late

Reetz K, Lischewski SA, Schulz JB, Praster M, Pishnamaz M; FACROSS study group; Dogan I, Romanzetti S, Dadsena R, Konrad K, Clavel T, Jankowski V, Jankowski J, Pabst O, Marx N, Moellmann J, Jacobsen M, Marx-Schütt K, Dukart J, Eickhoff S, Hilgers RD. Scoliosis Surgery in a Patient With Advanced Friedreich's Ataxia-It Is Not Too Late. Ann Clin Transl Neurol. 2025 Oct 3. doi: 10.1002/acn3.70219. Epub ahead of print. PMID: 41044041. 

 This case highlights the potential for substantial clinical and functional benefits from scoliosis surgery in patients with advanced Friedreich's ataxia.

From Mutations to Microbes: Investigating the Impact of the Gut Microbiome on Repeat Expansion Disorders

Das S, Patel M, Khandelwal S, Rawat R, Shukla S, Kumari AP, Singh K, Kumar A. From Mutations to Microbes: Investigating the Impact of the Gut Microbiome on Repeat Expansion Disorders. J Neurochem. 2025 Nov;169(11):e70278. doi: 10.1111/jnc.70278. PMID: 41194479. 

 Alterations in microbial diversity and composition have been observed across multiple REDs; however, a comprehensive understanding of the complete scenario remains a significant challenge. To elucidate these dynamic interactions, future research should utilize multifaceted approaches. This review focuses on the key modifications in the gut microbiome that contribute to the pathogenesis of REDs and discusses potential gut microbiome-targeted therapeutic strategies that could be effectively employed to treat these disorders.

Mitochondria-Mediated Mechanisms of Ferroptosis in Neurological Diseases

Zhong R, Yang H, Li X, Wang F, Zhai L, Gao J. Mitochondria-Mediated Mechanisms of Ferroptosis in Neurological Diseases. Neurochem Res. 2025 Nov 10;50(6):354. doi: 10.1007/s11064-025-04605-6. PMID: 41212342. 

This review first comprehensively explores the multifaceted mechanisms by which mitochondria mediate ferroptosis in neurological diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Friedreich's ataxia (FRDA), amyotrophic lateral sclerosis (ALS), epilepsy, stroke, and brain injury, with a focus on mitochondrial lipid peroxidation and iron metabolism dysregulation. Building on these mechanistic insights, we further discuss emerging evidence suggesting that targeting mitochondrial pathways may represent a promising therapeutic strategy for mitigating ferroptosis-associated neuronal damage. By synthesizing these findings, our review establishes a conceptual foundation for developing innovative neuroprotective interventions through precise modulation of mitochondrial function within ferroptotic pathways.

Cracking the code: a head-to-head comparison of expert clinicians and artificial intelligence in diagnosing rare diseases

Sendtner, G.W., Muecke, M., Grigull, L. et al. Cracking the code: a head-to-head comparison of expert clinicians and artificial intelligence in diagnosing rare diseases. Orphanet J Rare Dis 20, 564 (2025). doi:10.1186/s13023-025-04112-5

In this study, we showed that the differential diagnostic tool “Isabel Healthcare” can assist in identifying patient diagnoses. However, discrepancies between the tool’s output and the interdisciplinary case conferences were observed, indicating that while “Isabel Healthcare” can aid clinicians when filtered input is applied, it may not yet be fully effective on its own. Our findings highlight the potential of tools like “Isabel Healthcare” in the diagnostic process but emphasize the essential role of clinicians in filtering and contextualizing medical information.

Deep learning-based 3D reconstruction of dentate nuclei in Friedreich’s ataxia from T2*weighted MR images

Trushal Sardhara, Ravi Dadsena, Roland C. Aydin, Ralf-Dieter Hilgers, Leon Horn, Jörg B. Schulz, Kathrin Reetz, Sandro Romanzetti, Imis Dogan, Stella A. Lischewski, Kerstin Konrad, Miguel Pishnamaz, Maximillian Praster, Thomas Clavel, Vera Jankowski, Joachim Jankowski, Oliver Pabst, Katharina Marx-Schütt, Nikolaus Marx, Julia Möllmann, Malte Jacobsen, Juergen Dukart, Simon Eickhoff, Deep learning-based 3D reconstruction of dentate nuclei in Friedreich’s ataxia from T2*weighted MR images, Machine Learning with Applications, 2025, 100790, ISSN 2666-8270, doi:10.1016/j.mlwa.2025.100790. 

 We present a transfer learning–based machine learning pipeline for automated DN segmentation that directly uses standard T2*-weighted Magnetic Resonance Imaging (MRI), which highlights the DN without additional processing, and is designed to perform robustly with limited annotated data.

Voyager Reports Third Quarter 2025 Financial and Operating Results

LEXINGTON, Mass., Nov. 10, 2025 (GLOBE NEWSWIRE) -- Voyager Therapeutics, Inc. (Nasdaq: VYGR), a biotechnology company dedicated to leveraging genetics to treat neurological diseases, today reported third quarter 2025 financial and operating results.

Neurocrine partnership update: Neurocrine has indicated that they expect to provide an update on the IND filing timelines for their Friedreich’s ataxia (FA) and GBA1 gene therapy programs by the end of 2025. These filings could enable the initiation of clinical trials in 2026, pending supportive outcomes from the ongoing GLP toxicology studies, acceptance of the INDs by the FDA, and Neurocrine’s internal strategic assessment. Additionally, Neurocrine initiated a preclinical toxicology study with the fourth development candidate in a gene therapy program partnered with Voyager, triggering a $3 million milestone payment that is owed to Voyager in the fourth quarter of 2025.

Larimar Therapeutics, Inc. Updates on Nomlabofusp Development

On November 10, 2025, Larimar Therapeutics, Inc. provided updates on its nomlabofusp clinical program and future plans.

Individualized exercise and NAD+ precursor supplementation in Friedreich’s Ataxia: a randomized controlled trial

Lin, Kimberly Y. and Lin, Kimberly Y. and Bucha, Anna and Bucha, Anna and McSweeney, Kara and McSweeney, Kara and Wade, Kristin L. and Wade, Kristin L. and Karaj, Antoneta and Tamaroff, Jaclyn and Tamaroff, Jaclyn and O'Malley, Shannon and O'Malley, Shannon and Chung, Nicole M. and Chung, Nicole M. and Cilenti, Nicolette A. and Cilenti, Nicolette A. and Wanner, Julianne and Wanner, Julianne and Adzika, Gabriel K. and Adzika, Gabriel K. and Mesaros, Clementina and Blair, Ian A. and Blair, Ian A. and Rojsajjakul, Teerapat and Rojsajjakul, Teerapat and Serai, Suraj and Serai, Suraj and Farmer, Jennifer and Farmer, Jennifer and Bryant, Kyle and Bryant, Kyle and Lu, Yingying and Lu, Yingying and Harhay, Michael and Harhay, Michael and Weber, David R. and Weber, David R. and Paridon, Stephen M. and Paridon, Stephen M. and Seifert, Erin and Putt, Mary E. and Zamani, Payman and Zamani, Payman and Baur, Joseph A. and Lynch, David R. and Lynch, David R. and McCormack, Shana E. and McCormack, Shana E., Individualized exercise and NAD+ precursor supplementation in Friedreich’s Ataxia: a randomized controlled trial. doi:10.2139/ssrn.5698224. 

Interpretation: NR plus exercise for 12 weeks was safe and increased cardiovascular fitness in children and adults with FRDA. Adding NR to exercise could be considered as part of a comprehensive treatment approach.

The Triple Flexion Response in Friedrich’s Ataxia

Saluja A, Sahib A, Yadav V (November 04, 2025) The Triple Flexion Response in Friedrich’s Ataxia. Cureus 17(11): e96080. doi:10.7759/cureus.96080 

The triple flexion response is a significant diagnostic clue highlighting the marked corticospinal tract involvement in advanced Friedrich's ataxia.

Solid Biosciences Reports Third Quarter 2025 Financial Results

CHARLESTOWN, MA, Nov. 03, 2025 FA

(SGT-212): Solid has activated the first clinical trial site and is currently screening participants for FALCON, a Phase 1b first-in-human clinical trial evaluating SGT-212 for the treatment of Friedreich’s ataxia. 

SGT-212 for Friedreich’s Ataxia (FA)

In October 2025, the Company activated the first clinical trial site and began participant screening for FALCON, a first-in-human, open-label, Phase 1b clinical trial of SGT-212. The trial is expected to enroll non-ambulatory and ambulatory adult participants living with FA in up to three cohorts and is designed to evaluate the safety and tolerability of systemic and bilateral intradentate nucleus (IDN) administration of SGT-212. SGT-212 is the first investigational gene therapy for FA to utilize a dual route of administration and is intended to promote restoration of therapeutic levels of the frataxin protein to address the neurologic, cardiac and systemic clinical manifestations of FA.

Solid Biosciences Reports Third Quarter 2025 Financial Results

Early experience on omaveloxolone in adult patients with Friedreich's ataxia: a real-world observational study

Lima SM, Caltagirone M, Messina C, Quartetti U, Rini N, D'Amico F, Brighina F, Di Stefano V. Early experience on omaveloxolone in adult patients with Friedreich's ataxia: a real-world observational study. J Neurol. 2025 Nov 1;272(11):742. doi: 10.1007/s00415-025-13487-1. PMID: 41176519. 

 Omaveloxolone seems to be safe and well-tolerated in adult FRDA patients in the real-life setting. No significant worsening of symptoms was observed with no signs of progression, as well as the improvement of inflammatory biomarkers after 24 weeks of treatment, but no predictive factors for the disease response have been identified. However, the short duration, and the small sample size limit the generalizability of the results. Further studies with longer observation are needed to clearly define the efficacy of omaveloxolone in FRDA.

Friedreich ataxia:

Subramony SH, Lynch DR. Friedreich Ataxia. Pediatr Neurol. 2025 Nov 1;174:148-154. doi: 10.1016/j.pediatrneurol.2025.10.020. Epub ahead of print. PMID: 41252802.

With the introduction of potential new therapy for Friedreich ataxia (FRDA), the disorder has taken on a new importance in the world of pediatric neurology. Originally described more than 150 years ago, large scale clinical studies have defined diagnostic criteria and the underlying mutation as a biallelic, unstable expansion of an intronic GAA repeat in chromosome 9. In this review, we summarize the clinical features, routine management, pathophysiology, and emerging therapies for this devastating disease. The recent approval of omaveloxolone makes recognition of FRDA and its treatment essential for all pediatric neurologists.