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.