Development of a secretable frataxin for enhanced efficacy in treating Friedreich’s Ataxia

Daniel M. DuBreuil, Michael Fleming, Yashvi Parikh, Mikaela Woo, Jie Bu, Swathi Ayloo, Ingeborg M. Langohr, Dinesh S. Bangari, Christian Mueller, Shyam Ramachandran, Development of a secretable frataxin for enhanced efficacy in treating Friedreich’s Ataxia, Molecular Therapy Advances, 2025, 201661, ISSN 3117-387X, doi:10.1016/j.omta.2025.201661. 

No disease-modifying therapies are approved for FA, and current gene therapy approaches fail to address the full disease, forcing patients to choose between cardiac protection or neurological benefit. Here, we present ‘Engineered Cross-Correction,’ in which the therapeutic protein is bioengineered for secretion, expanding the therapeutic footprint. We apply this approach to FA by engineering a secretable frataxin and delivering it via a single intra-cerebrospinal fluid (CSF) injection of an adeno-associated viral (AAV) vector equipped with a novel capsid and tissue-selective promoter. We achieved broad protein repletion across key target tissues—heart, dorsal root ganglia, and cerebellum—in mouse and non-human primate. In FA mouse models, we observed rescue of cardiac and neurological phenotypes, marking the first demonstration of dual correction with a single, minimally invasive administration. These benefits were achieved without widespread transduction, reducing vector burden and associated toxicity. Our findings establish a scalable platform that contrasts with intravenous BBB-penetrant gene delivery and offers a generalizable strategy for multi-system disorders. Beyond FA, this positions Engineered Cross-Correction as a new frontier for the next generation of gene therapies.

Using a discrete choice experiments to explore societal preferences for valuing new drugs for rare diseases

Vargas, C., Goodall, S., Street, D.J. et al. Using a discrete choice experiments to explore societal preferences for valuing new drugs for rare diseases. Orphanet J Rare Dis 20, 631 (2025). doi:10.1186/s13023-025-04141-0 

Results In general, respondents had a greater preference for drugs that increase survival, where there was greater confidence in the effectiveness of the new drug and which increased patients’ capacity to do their usual activities. Preferences were not homogenous, the latent class analysis identified three groups: Class 3 (58%) demonstrated a strong preference for improvements in survival; Class 2 (21%) showed a strong preference for confidence in the evidence; and Class 1 (21%) positively valued increased government expenditure. 

Conclusion These results are consistent with previous studies that used different methodologies in showing a preference for drugs with improved survival and quality of life. However, addressing a societal preference for greater confidence in the evidence - reducing evidential uncertainty - represents a methodological and policy challenge for the evaluation of drugs in rare diseases.

Progressive scoliosis in a pediatric patient with cerebellar ataxia: surgical challenges and literature review

Asunis E, Vitulli F, Nicotra R, Rubino A, Cicala D, Cinalli G, Colella G. Progressive scoliosis in a pediatric patient with cerebellar ataxia: surgical challenges and literature review. Childs Nerv Syst. 2025 Dec 15;41(1):418. doi: 10.1007/s00381-025-07091-x. PMID: 41396316. 

 Spinal fusion can be performed safely in pediatric SCA/FA patients when meticulous multidisciplinary planning, individualized neuromonitoring strategies, and aggressive postoperative rehabilitation are adopted. Early recognition of underlying ataxia is critical for risk stratification and the timing of intervention. Prospective, longitudinal studies are warranted to refine guidelines and optimize neurological and orthopedic results in this complex population.

Digital Gait Measures Discriminate People with Friedreich's Ataxia from Healthy Controls

Casey HL, Shah VV, Muzyka D, McNames J, El-Gohary M, Sowalsky K, Safarpour D, Carlson-Kuhta P, Schmahmann JD, Rosenthal LS, Perlman S, Rummey C, Horak FB, Gomez CM. Digital Gait Measures Discriminate People with Friedreich's Ataxia from Healthy Controls. Mov Disord Clin Pract. 2025 Dec 17. doi: 10.1002/mdc3.70465. Epub ahead of print. PMID: 41408995. 

Digital gait measures from wearable sensors were discriminative, reliable, and showed concurrent validity for evaluating ataxia severity during an instrumented walk test. These results suggest promising utility of digital gait outcomes for use in FRDA clinical trials.

Neuropathology of Friedreich ataxia and its links to metabolic pathways

Mercado-Ayón E, Lazaropoulos MP, Mercado-Ayón Y, Lynch DR. Neuropathology of Friedreich ataxia and its links to metabolic pathways. Neurodegener Dis Manag. 2025 Dec 25:1-12. doi: 10.1080/17582024.2025.2607957. Epub ahead of print. PMID: 41447358. 

This review highlights recent insights into the neuropathology of FRDA, emphasizing the detailed developmental timing of neuroanatomical changes. It also focuses on selective mitochondrial metabolic pathways, including fatty acid metabolism, ceramide synthesis, and ketogenesis, which may underlie neuron-specific vulnerability and serve as potential targets for pharmacological or dietary intervention. The possibility of non-traditional interventions based on metabolic features of FRDA offers hope for ameliorating the severity of FRDA.

Unrecognized high prevalence of expanded composite repeats in Friedreich ataxia

Devore MC, Lam C, Wiley G, Park CC, Lynch DR, Bidichandani SI. Unrecognized high prevalence of expanded composite repeats in Friedreich ataxia. Hum Mol Genet. 2025 Dec 23:ddaf190. doi: 10.1093/hmg/ddaf190. Epub ahead of print. PMID: 41432640. 

In a prospective series of 112 unrelated patients, we found that approximately 20% of people with Friedreich ataxia have at least one such expanded composite allele. Other minor sequence interruptions in the expanded GAA repeat were detected in a further 10% of patients. Most expanded composite alleles revealed by longread genome sequencing are not detectable by standard PCR-based testing, and have therefore remained hidden despite their relatively high prevalence. This results in erroneous genotyping of patients and heterozygous carriers.

(Italy). The first treatment (Skyclarys) for Friedreich's ataxia will be reimbursed by the National Health Service

At its meeting on 15 December, the AIFA Board of Directors gave the green light to the reimbursement of Skyclarys (omaveloxolone), an orphan drug for the treatment of Friedreich's ataxia.

Skyclarys, the first medicine proven to slow the progression of the disease, was authorised by the European Medicines Agency (EMA) in February 2024 and included by AIFA in July 2024 in the list of medicines distributed under Law No. 648/1996, an early access programme that allows free dispensing to eligible patients, with the cost entirely covered by the National Health Service. Now, following negotiations with the marketing authorisation holder, the medicine will be available for reimbursement for the treatment of patients aged 16 years and older, upon prescription by centres for the treatment of rare diseases.

Respiratory Function in Friedreich's Ataxia

Viana CF, Jaques CS, Bezerra MLE, Barsottini OGP, Pedroso JL. Respiratory Function in Friedreich's Ataxia. Mov Disord. 2025 Dec 19. doi: 10.1002/mds.70162. Epub ahead of print. PMID: 41416841. 

FA patients exhibited significantly reduced forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1), alongside decreased maximal respiratory pressures (P < 0.01). A restrictive ventilatory pattern predominated. Peripheral oxygen saturation was lower in the FA group (P < 0.01). 

Respiratory impairment appears mostly subclinical, suggesting that FA patients may be vulnerable to pulmonary infections and ventilatory failure. This dysfunction may reflect both neuromuscular weakness and impaired respiratory coordination. Early and regular respiratory assessment, together with preventive and rehabilitative strategies integrated into multidisciplinary care, may improve quality of life and potentially prolong survival in individuals with FA.

Ferroptosis is a novel pathogenic mechanism of FDXR-related disease via disruption of the NRF2 pathway

Campbell, T., Slone, J., Vu, J. et al. Ferroptosis is a novel pathogenic mechanism of FDXR-related disease via disruption of the NRF2 pathway. Cell Death Discov. 11, 563 (2025). doi:10.1038/s41420-025-02840-y  

Our results suggest that ferroptosis is a novel underlying mechanism of FDXR-related disease and that activation of NRF2 could be an immediate, viable treatment option for individuals with FDXR-related disease and other conditions involving aberrant iron metabolism.

Targeting Friedreich Ataxia: A Sustainable Path to Safer and Smarter Therapeutics Through Integrated Docking and Toxicology

H. B. Attel, R. P, A. K, B. S, Shivandappa and S. Manokaran, "Targeting Friedreich Ataxia: A Sustainable Path to Safer and Smarter Therapeutics Through Integrated Docking and Toxicology," 2024 8th International Conference on Computational System and Information Technology for Sustainable Solutions (CSITSS), Bengaluru, India, 2024, pp. 1-4, doi: 10.1109/CSITSS64042.2024.10816941. 

 Our study aims to develop novel therapeutic candidates by leveraging computational protein-ligand docking through the Galaxy EU platform, targeting frataxin deficiencies. High-throughput docking and toxicology studies have identified several promising compounds with potential therapeutic efficacy, offering hope for more effective and sustainable treatments for FA.

The NCPE recommends that omaveloxolone not be considered for reimbursement

NCPE assessment completed, 16/12/2025. The National Centre for Pharmacoeconomics (NCPE) is a team of experts who look at the health benefits and costs of medicines. The HSE asks us to advise on whether or not a new medicine is good value for money. We give unbiased advice to help the HSE provide the most effective, safe and cost-effective (value for money) treatments for patients. 

After reviewing the data presented by the pharmaceutical company, we recommend that the HSE consider not providing omaveloxolone. This is because we are unsure based on the available clinical evidence that omaveloxolone leads to meaningful improvements in Friedreich’s ataxia symptoms. The current price of the medicine is too high, and there is no price at which omaveloxolone can be cost effective. We believe that the medicine is very poor value for money.

Cross-regulation of [2Fe–2S] cluster synthesis by ferredoxin-2 and frataxin

Want, K., Gorny, H., Turki, E. et al. Cross-regulation of [2Fe–2S] cluster synthesis by ferredoxin-2 and frataxin. Nature (2025). doi: 10.1038/s41586-025-09822-1 

 Using an in-vitro-reconstituted human system, we show that any deviation from a close-to-equal amount of FXN and FDX2 downregulates Fe–S cluster synthesis. Structure–function investigation reveals that this is due to competition between FXN and FDX2 and their similar affinities for the same binding site on the NFS1–ISCU2 complex, with higher levels of FXN impairing the persulfide reductase activity of FDX2 and higher levels of FDX2 slowing the FXN-accelerated transfer of persulfide to ISCU2. We also find that FDX2 directly hinders persulfide generation and transfer to ISCU2 by interacting with the persulfide-carrying mobile loop of NFS1. We further show that knocking down the expression of FDX2 increases fly lifespan in a Drosophila model of Friedreich’s ataxia. Together, this work highlights a direct regulation of Fe–S cluster biosynthesis through antagonistic binding of FXN and FDX2, and suggests that decreasing FDX2 in the context of FXN deficiency in Friedreich’s ataxia might constitute a novel therapeutic axis.

Mutations in mitochondrial ferredoxin FDX2 suppress frataxin deficiency

Meisel, J.D., Joshi, P.R., Spelbring, A.N. et al. Mutations in mitochondrial ferredoxin FDX2 suppress frataxin deficiency. Nature (2025). doi:10.1038/s41586-025-09821-2 

We show that lowering levels of wild-type FDX2 through loss of one gene copy can ameliorate the growth of frataxin mutant C. elegans or the ataxia phenotype of a mouse model of Friedreich’s ataxia under normoxic conditions. These genetic and biochemical studies indicate that restoring the stoichiometric balance of frataxin and FDX2 through partial knockdown of FDX2 may be a potential therapy for Friedreich’s ataxia.

Eli Lilly (LLY) Completes Acquisition of Adverum Biotechnologies

Eli Lilly (LLY) Completes Acquisition of Adverum Biotechnologies. GuruFocus News 12/09/2025. 

This acquisition enhances Eli Lilly's portfolio, which also includes promising candidates for retinitis pigmentosa and Friedreich's ataxia.

Solid Biosciences Receives FDA Rare Pediatric Disease Designation for SGT-212 Dual Route of Administration Gene Therapy for Friedreich’s Ataxia

CHARLESTOWN, Mass., Dec. 01, 2025 (GLOBE NEWSWIRE) -- Solid Biosciences Inc. today announced that it received Rare Pediatric Disease designation from the U.S. Food and Drug Administration (FDA) for SGT-212, the Company’s investigational gene therapy for Friedreich’s ataxia (FA). SGT-212 will deliver the full-length frataxin gene via dual routes of administration, utilizing both direct intradentate nucleus (IDN) and intravenous (IV) infusions, and was designed to promote restoration of therapeutic levels of the frataxin protein to address neurologic, cardiac and systemic clinical manifestations of FA.

Together with the Fast Track designation granted earlier this year, it recognizes our dual-route clinical approach for FALCON, our first-in-human trial, which is now screening participants, as an important first step in meeting an unmet need for FA. These designations are designed to help accelerate time to market and enhance engagement with the FDA. We look forward to continued collaboration with regulators to bring this therapy to patients as quickly as possible.

Enhancing the Objective Assessment of Friedreich Ataxia Severity: A Multiview IMU-Based Approach

Ranaweera K, Nguyen BA, Pathirana PN, Milne SC, Horne M, Delatycki MB, Corben LA. Enhancing the Objective Assessment of Friedreich Ataxia Severity: A Multiview IMU-Based Approach. Annu Int Conf IEEE Eng Med Biol Soc. 2025 Jul;2025:1-6. doi: 10.1109/EMBC58623.2025.11253596. PMID: 41335798. 

These findings indicate that multiview IMU-based systems can provide sensitive and reliable assessments of severity of ataxia in FRDA.Clinical relevance-This study presents a multiview IMU-based approach that can enhances the objective assessment of severity of ataxia in FRDA.

Reliable Objective Assessment of Friedreich Ataxia Through Isolation Forest-Based Anomaly Detection

Ranaweera K, Randeniya M, Pathirana PN, Milne SC, Horne M, Delatycki MB, Corben LA. Reliable Objective Assessment of Friedreich Ataxia Through Isolation Forest-Based Anomaly Detection. Annu Int Conf IEEE Eng Med Biol Soc. 2025 Jul;2025:1-6. doi: 10.1109/EMBC58623.2025.11253335. PMID: 41336277.

Clinical relevance- This study improves the reliability of objective Friedreich's ataxia assessments, providing clinicians with a more consistent and accurate tool for tracking disease progression and evaluating treatment effects.

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.

Drivers of managed entry agreements to reduce reimbursement challenges of orphan medicinal products: the development of a matrix

Callenbach, M.H.E., van den Berg, S., Hulsbosch, A. et al. Drivers of managed entry agreements to reduce reimbursement challenges of orphan medicinal products: the development of a matrix. Orphanet J Rare Dis 20, 540 (2025). doi:10.1186/s13023-025-04020-8 

"New orphan medicinal products (OMPs) are increasingly expensive and approved with limited clinical evidence". 

The matrix provides a systematic approach applied to mitigate clinical and cost-effectiveness uncertainties and/or reimbursement challenges specific to OMPs through advising MEAs. This study highlights the diversity in the drivers of MEAs to reduce risk and reimbursement challenges specific to OMPs and underscores the relevance of considering both established and innovative MEAs to address these.

Positron emission tomography reveals increased myocardial glucose uptake in a subset of Friedreich ataxia patients

Payne, R.M., O’Connell, T.M., Pride, P.M. et al. Positron emission tomography reveals increased myocardial glucose uptake in a subset of Friedreich ataxia patients. Sci Rep 15, 37247 (2025). https://doi.org/10.1038/s41598-025-21330-w 

 In this cohort of FRDA patients, a PET scan identified two metabolically distinct subclasses of FRDA cardiomyopathy. FRDA patients with severe LVH had greater FDG uptake relative to palmitate utilization than FRDA patients without severe LVH. FRDA patients with severe LVH have systolic and diastolic dysfunction, as well as ongoing cardiac damage as indicated by cTnI leak. These findings suggest that FRDA patients with significant LVH may be at increased risk of complications from surgery or major illness.

Development of an AAV-Based Gene Therapy for the Ocular Phenotype of Friedreich’s Ataxia

Tang H, Gupte S, Xu E, Calabro KR, Friend H, Crosson SM, Fajardo D,Kostamo Z, Zhang H, Peterson JJ, Lin F, Kozmik Z, Lutz CM, Boye SL, Boye SE, Development of an AAV-Based Gene Therapy for the Ocular Phenotype of Friedreich’s Ataxia, Molecular Therapy (2025), doi:10.1016/j.ymthe.2025.10.048.

Gene supplementation via intravitreal injection of a novel AAV2-based capsid carrying FXN partially preserved retinal structure and/or function in both models, establishing proof-of-concept for this therapeutic strategy.

Neuropsychiatric challenges of Friedreich ataxia in a patient residing in a long-term care facility

Wong J, Kwok J, Kim K. Neuropsychiatric challenges of Friedreich ataxia in a patient residing in a long-term care facility. Prim Care Companion CNS Disord 2025;27(5):25cr03965. doi:10.4088/PCC.25cr03965 

 The neuropsychiatric manifestations of FA are often under-recognized despite their significant impact on patient care and quality of life. This case underscores the necessity for comprehensive management strategies that address both the neurological and behavioral aspects of FA. This patient residing in a long-term care facility exhibited chronic depression and significant behavioral challenges including refusal of food, medications, and nursing care, alongside physical aggression. Despite initial treatment with citalopram, behavioral symptoms persisted while the neurovegetative signs of depression improved. As the escalation of the patient’s behavioral symptoms marked a critical turning point, divalproex ER was introduced and titrated to manage his mood instability. Subsequently, the patient’s mood and behavior symptoms noticeably improved without worsening motor dysfunction, highlighting the importance of personalized psychopharmacologic interventions.

Jupiter Neurosciences, Inc. strategic partnership with Zina Biopharmaceutica

October 22, 2025. The company develops JNS101, which is in Phase II trial for the treatment of Friedreich's Ataxia, a rare inherited disease that causes damage to the nervous system, as well as mobility dysfunctions; and JNS108 that is in Phase II trial for treating mild cognitive impairment/early Alzheimer’s disease. It is also involved in the development of JNS102, which is in Phase II trial for the treatment of mucopolysaccharidosis type 1; and JNS107 that is in Phase II trial for treating mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes syndrome. In addition, the company develops JNS115, which is in Phase IIa trial for the treatment of Parkinson’s disease. It has a strategic partnership with Zina Biopharmaceuticals, LLC to advance Phase 2a clinical trial to evaluate the safety, tolerability, and pharmacokinetics of Resveratrol (JOTROLTM) in individuals with Parkinson’s disease; and with Aquanova AG to develop a series of consumer-focused nutritional products targeting longevity, aging, and healthspan. The company was formerly known as Jupiter Orphan Therapeutics, Inc. and changed its name to Jupiter Neurosciences, Inc. in August 2021. Jupiter Neurosciences, Inc. was incorporated in 2016 and is headquartered in Jupiter, Florida.

Exploring the pleiotropic effects of lncRNA in different repeat expansion disorders

Soumalya Das, Shubhi Khandelwal, Sakshi Shukla, Amit Kumar, Exploring the pleiotropic effects of lncRNA in different repeat expansion disorders, Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2025, 168089, ISSN 0925-4439, doi:10.1016/j.bbadis.2025.168089.

A Probabilistic Deep Ensemble Framework for the Objective Assessment of Friedreich Ataxia

Maneesha Randeniya, Kanishka Ranaweera, Thang Ngo, et al. A Probabilistic Deep Ensemble Framework for the Objective Assessment of Friedreich Ataxia. TechRxiv. October 16, 2025. DOI: 10.36227/techrxiv.176062677.75204670/v1

There was strong agreement between the proposed ensemble and clinical mFARS scores, reflected in a Pearson correlation of 0.81, Spearman's correlation of 0.76, R² of 0.46, RMSE of 10.30, and MAE of 8.79 on the unseen test set. Uncertainty was systematically evaluated using Uncertainty Characteristics Curves (UCC), where the ensemble achieved an Area Under UCC (AUUCC) of 8.83.

Chapter 23 - Omaveloxolone: a nuclear factor erythroid 2-related factor 2 activator for Friedreich’s ataxia

Ziquan Zhao, Junjie Wang, Mengchen Lu, Qidong You, Zhengyu Jiang, Chapter 23 - Omaveloxolone: a nuclear factor erythroid 2-related factor 2 activator for Friedreich’s ataxia, Editor(s): Bin Yu, Peng Zhan, Drug Discovery Stories, Volume 2, Elsevier, 2026, Pages 331-344, ISBN 9780443338854, doi:10.1016/B978-0-443-33885-4.00038-X. 

 Nuclear factor erythroid 2-related factor 2 (NRF2) is an important cytoprotective transcription factor that affects the fate of the cell. Impairment of the NRF2 signaling pathway has been regarded as a major contributor to the pathophysiology of FRDA, and targeting NRF2 activation has become an attractive strategy for the treatment of FRDA.

Targeting rare splicing defects: Antisense oligonucleotides offer a therapeutic strategy in FRDA

Targeting rare splicing defects: Antisense oligonucleotides offer a therapeutic strategy in FRDA, Kerkhof, Laurie M.C. et al., Molecular Therapy Nucleic Acids, Volume 36, Issue 4, 102723 doi:10.1016/j.omtn.2025.102723

Using patient-derived cells, the authors demonstrated that antisense oligonucleotides (ASOs) targeting splicing regulatory elements effectively restore splicing deficits and increase frataxin expression. While encouraging in cell-based studies, this strategy is limited to a small subset of individuals with FRDA carrying these rare mutations and requires functional validation in disease-relevant tissues.

Analysis of a Modified Version of the Inventory of Non-Ataxia Signs Over 12 Years in Patients with Friedreich's Ataxia in the EFACTS Study

Lischewski, S.A., Dogan, I., Giunti, P., Parkinson, M.H., Mariotti, C., Durr, A., Ewenczyk, C., Boesch, S., Nachbauer, W., Klopstock, T., Stendel, C., de Rivera Garrido, F.J.R., Schöls, L., Fleszar, Z., Klockgether, T., Grobe-Einsler, M., Giordano, I., Rai, M., Pandolfo, M., Jacobi, H., Hilgers, R.-D., Schulz, J.B., Reetz, K. and the EFACTS Study Group (2025), Analysis of a Modified Version of the Inventory of Non-Ataxia Signs Over 12 Years in Patients with Friedreich's Ataxia in the EFACTS Study. Mov Disord. doi:10.1002/mds.70084

Participants were drawn from the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS). The modified INAS count (presence/absence, 0–16 scale) and modified INAS sum (severity-weighted, 0–84 scale) were evaluated using linear mixed-models and standardized response means (SRMs). Items rare (<5%) and uncharacteristic in Friedreich's ataxia were excluded (chorea, myoclonus, fasciculations, resting tremor, rigidity)

LEXEO Message to the Friedreich Ataxia Community

Message to the Friedreich Ataxia Community. October 7, 2025​.

This morning, we were pleased to share positive interim clinical data for LX2006, our investigational gene therapy, that includes both cardiac and neurological outcome measures. LX2006 (AAVrh10hFXN) is currently being studied in the Lexeo-sponsored SUNRISE-FA Phase 1/2 clinical trial and the Weill Cornell Medicine investigatorinitiated Phase 1A trial for the treatment of Friedreich ataxia cardiomyopathy.

Frataxin depletion leads to decreased soma size and activation of AMPK metabolic pathway in dorsal root ganglia sensory neurons

Frataxin depletion leads to decreased soma size and activation of AMPK metabolic pathway in dorsal root ganglia sensory neurons Olivier Griso, Deepika Mokkachamy Chellapandi, Amelie Weiss, Ioannis Manolaras, Helene Puccio. bioRxiv 2025.10.07.680891; doi:10.1101/2025.10.07.680891 

Our findings uncover AMPK-mTOR dysregulation as a key driver of neuronal growth impairment in FA. This robust neuronal model provides new insights into proprioceptive neuron vulnerability and offers a platform for therapeutic discovery.

Synthesis and Biological Profile of Omaveloxolone: The Cornerstone for Friedreich Ataxia Treatment

Cordaro, M.; Neri, G.; Ansari, S.A.M.K.; Buccheri, R.; Scala, A.; Piperno, A. Synthesis and Biological Profile of Omaveloxolone: The Cornerstone for Friedreich Ataxia Treatment. Int. J. Mol. Sci. 2025, 26, 9747. doi:10.3390/ijms26199747 

This review provides a comprehensive overview of the therapeutic potential of omaveloxone (OMA) for the treatment of Friedreich’s ataxia (FA), along with an analysis of the historical development and current status of the synthetic strategies for OMA production. OMA activates the nuclear factor-2-(erythroid-2)-related (Nrf2) pathway in vitro and in vivo, in both animal models and humans. The Nrf2 pathway plays a crucial role in the cellular response to oxidative stress. Furthermore, OMA has been shown to mitigate mitochondrial dysfunction, restore redox homeostasis and downregulate nuclear factor-κB (NF-κB), a key mediator of inflammatory responses. Through these mechanisms, OMA contributes to tissue protection and inflammation reduction in patients with FA. The review also highlights future perspective, focusing on the challenges associated with OMA reprofiling through innovative drug delivery approaches and its potential repurposing for diseases beyond FA.

Lexeo Therapeutics Stock Rallies On Discussions With FDA To Expedite Friedreich’s Ataxia Drug Approval Process

Published Oct 07, 2025. https://stocktwits.com 

The company stated that data from a planned pivotal study will be pooled with data from the ongoing Phase I/II studies of LX2006 to support an approval application to the U.S. Food and Drug Administration for the therapy. 

 Lexeo Therapeutics (LXEO) announced on Tuesday that the company is considering a smaller pivotal study for LX2006 in the treatment of Friedreich's ataxia (FA) cardiomyopathy, scheduled to begin in the first half of 2026, pending finalization of the study protocol. 

 The data from the planned pivotal study will be pooled with data from the ongoing Phase I/II studies of LX2006 to support an approval application to the U.S. Food and Drug Administration for the therapy, the company stated after discussions with the agency.

Lexeo says FDA open to speedier approval of rare disease gene therapy

Published Oct. 7, 2025. https://www.biopharmadive.com/ 

The agency will consider a submission that includes pooled data from ongoing studies, a decision analysts viewed as a notable, additional sign of regulatory flexibility for gene therapies.

According to the company, the agency has “indicated openness” to an accelerated approval filing for its treatment — a gene therapy called LX2006 for the neurodegenerative condition Friedreich’s ataxia — that’s based on pooled data from ongoing studies as well as results from a planned pivotal trial.

A25-86 Omaveloxolone (Friedreich’s ataxia) – Benefit assessment according to §35a Social Code Book V

Commission awarded on 01.07.2025 by the Federal Joint Committee (G-BA). Last updated 01.10.2025. 

Result of dossier assessment: Added benefit not proven.

Delphi study to elicit expert consensus around decision-making in the treatment of Friedreich ataxia

Delphi study to elicit expert consensus around decision-making in the treatment of Friedreich ataxia. Front. Neurol.Sec. Movement Disorders Volume 16 - 2025 | doi: 10.3389/fneur.2025.1669059

Consensus was reached on a portion of questions regarding FA diagnosis and assessment, perhaps due to the rarity of disease and panelists' varying FA experience. To improve and standardize management of FA, it is important to establish best practices and educate potential FA treaters as new therapies emerge.

357PLong-term vatiquinone treatment slows Friedreich’s ataxia disease progression relative to FACOMS natural history

357PLong-term vatiquinone treatment slows Friedreich’s ataxia disease progression relative to FACOMS natural history. Vagabov, A. et al. Neuromuscular Disorders, Volume 53, 106087 DOI:10.1016/j.nmd.2025.106087 

 The results of the extension studies provide further evidence of the potential benefit of vatiquinone for the treatment of FA. The pre-specified endpoints for two different long-term extension studies were met, with highly statistically significant evidence of durable treatment benefit in slowing disease progression in paediatric and adult patients.

234PLong-term use of omaveloxolone in patients with Friedreich ataxia: up to 5 years of natural history propensity score matching from the MOXIe OLE

234PLong-term use of omaveloxolone in patients with Friedreich ataxia: up to 5 years of natural history propensity score matching from the MOXIe OLE. Nachbauer, W. et al.. Neuromuscular Disorders, Volume 53, 106043 doi:10.1016/j.nmd.2025.106043 

 Continued analysis of the MOXIe OLE data informs on long-term efficacy and safety of omaveloxolone in patients with FA and provides relevant insights regarding disease progression in patients treated with omaveloxolone relative to the natural pattern of FA progression in the FACOMS cohort.

Friedreich Ataxia and Related Diabetes: Therapeutic Approach Targeting Mitochondrial Dysfunction

Pichakacheri Sureshkumar, Sidharth S Kumar, Johny Cheriyan, Asif Masood, Friedreich Ataxia and Related Diabetes: Therapeutic Approach Targeting Mitochondrial Dysfunction, JCEM Case Reports, Volume 3, Issue 11, November 2025, luaf215, doi:10.1210/jcemcr/luaf215 

 This case report discusses a 32-year-old woman with Friedreich ataxia (FA) and suboptimally managed diabetes mellitus (DM), focusing on a treatment strategy aimed at improving mitochondrial function for better glycemic control and symptom management. Her regimen included insulin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, neurotropic vitamins, and mitochondriotropic agents and antioxidants, specifically L-carnitine, coenzyme Q10 (CoQ10), and vitamin E. Imeglimin, a mitochondriotropic antihyperglycemic agent, was also part of her regimen.

357P Long-term vatiquinone treatment slows Friedreich’s ataxia disease progression relative to FACOMS natural history

A. Vagabov, J. Cherry, A. Duqette, M. França, S. Perlman, A. Durr, E. Bertini, K. Mathews, L. Schöls, A. Fournier, M. Delatycki, S. Subramony, R. Roxburgh, M. Rance, O. Zhang, L. Golden, J. Gruenert, C. Werner, D. Lynch, T. Zesiewicz, 357PLong-term vatiquinone treatment slows Friedreich’s ataxia disease progression relative to FACOMS natural history, Neuromuscular Disorders, Volume 53, Supplement, 2025, 106087, ISSN 0960-8966, doi:10.1016/j.nmd.2025.106087. 

 Vatiquinone (EPI-743) is an investigational, oral, first-in-class 15-lipoxygenase inhibitor being developed for the treatment of patients with Friedreich’s ataxia (FA). Here, we report long-term results of vatiquinone treatment in patients with FA from the MOVE-FA extension study (36 months) and Study EPI-2010-006 (24 months), compared with matched natural history cohorts from FACOMS (Friedreich Ataxia Clinical Outcome Measures). MOVE-FA (NCT04577352) was a global phase 3 study of vatiquinone in patients with FA aged ≥ 7 years (N = 143; mean age: 18.7 years); participants who completed MOVE-FA were eligible to rollover into the long-term extension (NCT05515536). EPI-2010-006 (NCT01728064) was a phase 2 study of vatiquinone in adult patients with FA ≥ 18 years (N = 63; mean age: 28.9 years). The pre-specified primary endpoint for these analyses was the modified Friedreich’s Ataxia Rating Scale (mFARS). After 36 months in the MOVE-FA long-term extension study, participants in the vatiquinone treatment group demonstrated a 3.75-point increase in mFARS. The matched FACOMS cohort progressed by 7.48 points over the same period. Vatiquinone treatment resulted in a 3.7-point benefit (p < 0.0001, n = 70) in mFARS relative to FACOMS, representing a clinically meaningful 50% slowing of disease progression over 3 years. Following 24-months of treatment with vatiquinone in EPI-2010-006, participants demonstrated a 0.92-point decrease in mFARS while participants in the matched FACOMS cohort progressed by 3.89 points. This resulted in a 4.8-point treatment benefit (p < 0.0001, n = 41), consistent with a 2-year delay in progression. The results of the extension studies provide further evidence of the potential benefit of vatiquinone for the treatment of FA. The pre-specified endpoints for two different long-term extension studies were met, with highly statistically significant evidence of durable treatment benefit in slowing disease progression in paediatric and adult patients.

Emerging therapies for Friedreich Ataxia and the prospect of future combination treatments

Lees, J. G., Li, L., & Lim, S. Y. (2025). Emerging therapies for Friedreich Ataxia and the prospect of future combination treatments. Future Rare Diseases, 5(1). doi:10.1080/23995270.2025.2563497

Although no single therapy has yet delivered a cure, the growing understanding of FRDA’s underlying mechanisms, coupled with an expanding therapeutic arsenal and more refined clinical measures, offers genuine hope that transformative, life-changing treatments are within reach. Realizing this promise will depend on continued collaboration among patients, clinicians, researchers, industry, and regulatory stakeholders to ensure that scientific advances translate into tangible, meaningful benefits for the FRDA community.

Larimar Therapeutics Announces Positive Data from Ongoing Long-term Open Label Study and Updates to Nomlabofusp Program for Friedreich’s Ataxia

BALA CYNWYD, Pa., Sept. 29, 2025 (GLOBE NEWSWIRE) -- Larimar Therapeutics, Inc. (Larimar) (Nasdaq: LRMR), a clinical-stage biotechnology company focused on developing treatments for complex rare diseases, today announced positive 25 mg and 50 mg data from the ongoing long-term open label (OL) study evaluating daily subcutaneous injections of nomlabofusp self-administered or administered by a caregiver in participants with Friedreich’s ataxia (FA), a rare, progressive, and systemic disease with neurologic deterioration. The Company also provided a nomlabofusp development program update.

Friedreich's Ataxia in Colombia: A Population-Based Study of Incidence and Socioeconomic Determinants

Correa-Arrieta C, Castellar-Leones S, Ruiz-Ospina E, Villamil-Osorio M, Bobadilla-Quesada EJ, Ortiz-Corredor F. Friedreich's Ataxia in Colombia: A Population-Based Study of Incidence and Socioeconomic Determinants. Mov Disord. 2025 Sep 19. doi: 10.1002/mds.70033. Epub ahead of print. PMID: 40970480. 

Ninety-two genetically confirmed cases were identified across 17 departments. Bogotá registered the most cases (32.6%), whereas Vichada showed the highest adjusted cumulative incidence (58.33 per million). The 10-19-year group accounted for the largest share of diagnoses (35.9%); 23.9% were diagnosed at ≥40 years. Marked social vulnerability was observed: 27.2% had no formal education and 60.9% were outside the labor force.

Impact of age on neurofilament light chain in Friedreich ataxia: a 1-year longitudinal study

Petrillo S, Mongelli A, Castaldo A, Sarro L, Azzarelli S, Ronco R, Castellotti B, Gellera C, Piemonte F, Mariotti C. Impact of age on neurofilament light chain in Friedreich ataxia: a 1-year longitudinal study. Brain Commun. 2025 Sep 10;7(5):fcaf331. doi: 10.1093/braincomms/fcaf331. PMID: 40994821; PMCID: PMC12455201. 

 Our study confirms the typical NfL profile in FRDA patients. Our data further support the role of NfL as early indicator of axonal damage and as potential pharmacodynamic biomarker of therapeutical response especially valuable in pediatric populations.

Leriglitazone improves iron homeostasis and ferroptotic markers in frataxin-deficient dorsal root ganglia neurons

Biomed Pharmacother . 2025 Sep 18:192:118553. doi: 10.1016/j.biopha.2025.118553. Online ahead of print. Leriglitazone improves iron homeostasis and ferroptotic markers in frataxin-deficient dorsal root ganglia neurons Marta Portillo-Carrasquer 1, Arabela Sanz-Alcázar 1, Fabien Delaspre 1, Maria Pazos-Gil 1, Luiza Oliveira-Jorge 1, Cristina Vergara 2, Laura Rodríguez-Pascau 3, Pilar Pizcueta 3, Jordi Tamarit 1, Joaquim Ros 1, Elisa Cabiscol 4  DOI: 10.1016/j.biopha.2025.118553

Type and position of repeat interruptions as determinants of disease severity and expansion size in Friedreich ataxia

Type and position of repeat interruptions as determinants of disease severity and expansion size in Friedreich ataxia, Benkirane, Mehdi et al., Genetics in Medicine, Volume 0, Issue 0, 101588 DOI: 10.1016/j.gim.2025.101588  

Three groups of FRDA patients were identified by the simultaneous analysis of the precise distance (“depth”) between the interruptions (mostly non-triplet) and the 3’ end of the expansion (P < 0.001), the smaller expansion size (P < 0.001), and AAO (P < 0.001). Classical FRDA corresponds to absence of interruption or interruption depth 18 (AUC = 0.97; 95% CI, 0.92-1) and AAO >34 years. Multiple (>5) triplet interruptions hamper further expansion.

Ataxia UK Stresses Urgent Action on Friedreich’s Ataxia Treatment Access

Ataxia UK has issued a press release today highlighting the urgent need for access to omaveloxolone (Omav), the only approved treatment for Friedreich’s ataxia (FA). Despite MHRA approval, people in England, Wales and Northern Ireland are still waiting, while in Scotland a pathway exists for clinicians to apply for early access on a case-by-case basis. The medicine is available for patients in the US and Europe. This inequality cannot continue. We are calling on the Department of Health and Social Care to work with us, clinicians, and the FA community on a temporary compassionate access programme before more time is lost.

Progress and challenges in sporadic late-onset cerebellar ataxias

Wirth, T., Faber, J., Depienne, C. et al. Progress and challenges in sporadic late-onset cerebellar ataxias. Nat Rev Neurol (2025). doi: /10.1038/s41582-025-01136-0 

The ongoing development and increased availability of DNA sequencing technology have uncovered several molecular causes of SLOCA besides spastic paraplegia type 7 and very late-onset Friedreich ataxia.

Megabase-scale human genome rearrangement with programmable bridge recombinases

Nicholas T. Perry et al. ,Megabase-scale human genome rearrangement with programmable bridge recombinases. Science 0, eadz0276 DOI:10.1126/science.adz0276 

Through rational engineering of the ISCro4 bridge RNA and deep mutational scanning of its recombinase, we achieved up to 20% insertion efficiency into the human genome and genome-wide specificity as high as 82%. We further demonstrated intrachromosomal inversion and excision, mobilizing up to 0.93 megabases of DNA. 

Lastly, we provided proof-of-concept for plasmid-based excision of disease-relevant gene regulatory regions or repeat expansions. 

As a proof-of-concept, the researchers created artificial DNA constructs containing the same toxic repeat sequences that cause progressive neuromuscular decline in Friedreich's ataxia patients. 

 While healthy individuals carry fewer than 10 sequential copies of a three-letter DNA sequence, people with the disorder can harbor up to 1,700 copies, which interferes with normal gene function. 

 The engineered ISCro4 successfully removed these repeats from the artificial constructs, in some cases eliminating over 80% of the expanded sequences.

A Digital Measure of Eye Movements During Reading Sensitively Captures Oculomotor and Speech Dysfunction, Early Changes, and Disease Progression in Ataxias

Oubre, B., Yang, F., Luddy, A.C., Manohar, R., Soja, N.N., Stephen, C.D., Schmahmann, J.D., Kulkarni, D., White, L., Patel, S. and Gupta, A.S. (2025), A Digital Measure of Eye Movements During Reading Sensitively Captures Oculomotor and Speech Dysfunction, Early Changes, and Disease Progression in Ataxias. Ann Neurol. doi:10.1002/ana.78039 

Digital measures of eye movements are a promising approach for sensitively measuring ataxia in clinical trials (including early-stage disease) and may have utility in other neurodegenerative diseases affecting speech or ocular control. 

Omaveloxolone (Skyclarys): Indication: For the treatment of Friedreich’s ataxia in patients 16 years of age and older: Reimbursement Recommendation [Internet]

Omaveloxolone (Skyclarys): Indication: For the treatment of Friedreich’s ataxia in patients 16 years of age and older: Reimbursement Recommendation [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2025 Jul. Report No.: SR0864. PMID: 40857368.

What Is the Reimbursement Recommendation for Skyclarys?: Canada’s Drug Agency (CDA-AMC) recommends that Skyclarys be reimbursed by public drug plans for the treatment of Friedreich’s ataxia (FA) if certain conditions are met.

Genetic and Phenotypic Variability in Siblings With Friedreich Ataxia

Eshaghi K, Rao PH, Shen MM, Lynch DR. Genetic and Phenotypic Variability in Siblings With Friedreich Ataxia. Neurol Genet. 2025 Jan 13;11(1):e200234. doi: 10.1212/NXG.0000000000200234. PMID: 40880907; PMCID: PMC11731371. 

Genetic and phenotypic variability between paired siblings with FRDA was moderate to small, with GAA1 differences explaining some of the variance in AAO. Other factors (genetic or environmental) or data collection bias may explain the remaining variance. These findings highlight the complexity of FRDA and reiterate the role of GAA1 length in disease severity.

Oxidative Stress and Antioxidant Therapies in Friedreich’s Ataxia

Jiménez-Jiménez, F.J.; Alonso-Navarro, H.; García-Martín, E.; Cárcamo-Fonfría, A.; Martín-Gómez, M.A.; Agúndez, J.A.G. Oxidative Stress and Antioxidant Therapies in Friedreich’s Ataxia. Cells 2025, 14, 1406. doi:10.3390/cells14181406 

Many antioxidant drugs have shown the ability to reduce oxidative stress in experimental models of FRDA. Therefore, these drugs may be useful in treating FRDA and are likely candidates for future clinical trials. Future studies investigating oxidative stress and antioxidant therapies in FRDA should adopt a prospective, multicenter, long-term, double-blind design.

Characterizing Population Pharmacokinetics of Vatiquinone in Healthy Volunteers and Patients with Friedreich’s Ataxia

Hu, Y.; Gao, L.; Lee, L.; Cherry, J.J.; Kong, R. Characterizing Population Pharmacokinetics of Vatiquinone in Healthy Volunteers and Patients with Friedreich’s Ataxia. Pharmaceuticals 2025, 18, 1339. doi:10.3390/ph18091339 

A two-compartment model effectively described the pharmacokinetic profiles of vatiquinone after oral administration. Covariates significantly impacted exposures, including body weight, meals, disease status, comedications and body mass index.

Repeat-associated ataxias in a German patient cohort analysed by targeted parallel long-read sequencing

Hannes Erdmann, Annalisa Schaub, Morghan C Lucas, Veronika Scholz, Anna Benet-Pages, Kerstin Becker, Christine Dineiger, Veronika Mayer, Inga van Buren, Eva Breithausen, Karl Akbari, Isabell Cordts, Mayra Sauer, Christine Schneider, Rosanna Krakowsky, Franziska Schnabel, Konstanze Dunker, Lena Fabritius, Johannes Gerb, Denis Grabova, Ken Möhwald, Marius Näher, Karoline Steinmetz, Franziska Thiessen, Alexander Jäck, Christiane Schneider-Gold, Simone Zittel, Christina Petersen, Isolde Schreyer, Larissa Mämecke, Sibylle Wilfling, Gilbert Wunderlich, David Brenner, Yorck Hellenbroich, Kirsten Muhle, Tessa Huchtemann, Inga Claus, Thomas Klopstock, Michael Strupp, Johannes Levin, Günter Höglinger, Doreen Huppert, Sandra Becker-Bense, Filipp Filippopulos, Fabian Kilpert, Elsa Leitão, Sabine Kaya, Christel Depienne, Florian Schöberl, Teresa Neuhann, Elke Holinski-Feder, Andreas Zwergal, Angela Abicht, Repeat-associated ataxias in a German patient cohort analysed by targeted parallel long-read sequencing, Brain, 2025;, awaf318, doi:10.1093/brain/awaf318 

We confirmed a high RFC1 spectrum disorder carrier frequency (7.2%) and reclassified certain FXN expansions as likely non-pathogenic, resulting in a lower than estimated carrier frequency for FRDA of 0.8% (1:125)

Design Therapeutics Faces Regulatory Hurdle While Maintaining Financial Stability

01.09.25 09:19, Börse Global (en). 

Clinical Program Pivot Following FDA Decision A significant development emerged from regulatory discussions with the U.S. Food and Drug Administration. The agency imposed a clinical hold on Design Therapeutics' planned expansion of its key RESTORE-FA study within the United States. This critical trial evaluates the promising drug candidate DT-216P2 as a treatment for Friedreich's ataxia, a progressive neurological disorder. While initial pharmacokinetic data had shown encouraging results, the FDA's decision has substantially delayed the program's advancement and raised questions about the regulatory path forward. Despite this setback in the U.S. market, the company continues to progress with the study outside American borders. 

Frataxin deficiency drives cardiac dysfunction and transcriptional dysregulation in Friedreich ataxia iPSC model

Frataxin deficiency drives cardiac dysfunction and transcriptional dysregulation in Friedreich ataxia iPSC model. Jarmon G. Lees, Haoxiang Zhang, Lebei Jiao, Anne M Kong, Ren Jie Phang, Li Li, Nan Su, Anthony S. Mukhtar, Alice Pébay, Mirella Dottori, Louise Corben, Martin Delatycki, Roger Peverill, Stephen Wilcox, Jarny Choi, Jeffrey M. Pullin, Davis McCarthy, Jill S. Napierala, Marek Napierala, Shiang Y. Lim bioRxiv 2025.08.20.671405; doi:10.1101/2025.08.20.671405 

This preclinical human model provides valuable insight into the pathogenesis of FRDA and provides a platform for developing early-stage therapeutic interventions.

In vivo gene therapy: A strategy for mutations, degenerations, and tumors

Tao Wang, Mingyang Yu, Ping Liu, Zhiqiang Song, Cheng Li, Jianmin Yang, Na Liu, In vivo gene therapy: A strategy for mutations, degenerations, and tumors, Genes & Diseases, 2025, 101808, ISSN 2352-3042, doi:10.1016/j.gendis.2025.101808. 

 The current review summarizes the development of DNA nucleases and delivery vectors for in vivo gene therapy, emphasizing recent progress.

Spatial perspective taking is impaired in spinocerebellar ataxias and Friedreich ataxia

Karamazovova, S., Laczó, M., Matuskova, V. et al. Spatial perspective taking is impaired in spinocerebellar ataxias and Friedreich ataxia. Sci Rep 15, 31126 (2025). doi:10.1038/s41598-025-16302-z 

This study aimed to investigate perspective taking in patients with SCA and Friedreich ataxia (FRDA) using two tests. The Perspective-Taking/Spatial Orientation Test (PTSOT) was administered to 30 SCA patients, 30 FRDA patients, and 34 healthy controls (HC). In addition, SCA and HC completed the Directional-approach Task and a comprehensive neuropsychological assessment. SCA patients performed significantly worse than HC on both perspective taking tests. FRDA patients performed better than SCA and differed from HC only in a subset of PTSOT measures. Perspective taking performance in SCA was associated with global cognition and multiple cognitive domains but not with cerebellar motor impairment.

Alpha–lipoic acid supplementation improves pathological alterations in cellular models of Friedreich ataxia

Talaverón-Rey, M., Reche-López, D., Povea-Cabello, S. et al. Alpha–lipoic acid supplementation improves pathological alterations in cellular models of Friedreich ataxia. Orphanet J Rare Dis 20, 453 (2025).doi:10.1186/s13023-025-03990-z 

 Treatment with ALA was able to correct partially the pathological alterations in mutant fibroblasts. The optimal ALA concentration was dependent on the number of expanded GAA triplet repeats in the FXN gene. The positive effect of ALA was also confirmed in induced neurons derived from FRDA mutant fibroblasts. Our results also suggest that the positive effect of ALA was mediated by Peroxisome Proliferator-Activated Receptor Gamma activation. 

Conclusions: Our results suggest that ALA treatment can increase the expression levels of frataxin and reverse the mutant phenotype in cellular models of FRDA.

 

PTC Therapeutics Receives Complete Response Letter for Vatiquinone NDA

WARREN, N.J., Aug. 19, 2025 /PRNewswire/ -- PTC Therapeutics, Inc., announced today that the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) related to the New Drug Application (NDA) for vatiquinone for the treatment of children and adults living with Friedreich's ataxia.

"We are of course disappointed by the FDA's decision to not approve vatiquinone," said Matthew B. Klein, M.D., Chief Executive Officer of PTC Therapeutics. "We believe the data collected to date demonstrate that vatiquinone could provide a safe and effective therapy for both children and adults living with Friedreich's ataxia. We plan to meet with the FDA to discuss potential steps to address the issues raised in the CRL.

" The FDA stated in the CRL that substantial evidence of efficacy was not demonstrated for vatiquinone and that an additional adequate and well-controlled study would be needed to support NDA resubmission.

Propensity-matched analysis comparing omaveloxolone treatment to Friedreich ataxia natural history data: a plain language summary

Lynch, D. R., Goldsberry, A., Rummey, C., Farmer, J., Boesch, S., Delatycki, M. B., … Meyer, C. (2025). Propensity-matched analysis comparing omaveloxolone treatment to Friedreich ataxia natural history data: a plain language summary. Future Neurology, 20(1). doi:10.1080/14796708.2025.2524313 

Friedreich ataxia (FA) is an inherited disorder that gets worse over time and affects movement, coordination, and speech. Omaveloxolone (Skyclarys®) capsules are a medicine that has been approved to treat FA in people aged 16 years and older. The approval is based on findings from the MOXIe clinical trial program. This program had 3 parts (Part 1, Part 2, and the MOXIe Open Label Extension). The MOXIe Part 2 study showed that omaveloxolone slowed the worsening of the disease in people with FA compared with those who received an inactive drug–or placebo–over 48 weeks (or 11 months). The study also showed that omaveloxolone causes side effects that were considered manageable, allowing most patients to continue using it.

Sensory nerve action potential reappearance after omaveloxolone treatment in patients with Friedreich ataxia

Sensory nerve action potential reappearance after omaveloxolone treatment in patients with Friedreich ataxia. Melita Rotar, Lea Leonardis; Clinical Neurophysiology Volume 178, October 2025, 2110974. doi:10.1016/j.clinph.2025.2110974 (Letter to the Editor).

Best Oculomotor Endpoints for Clinical Trials in Hereditary Ataxias: A Systematic Review and Consensus by the Ataxia Global Initiative Working Group on Digital‑Motor Biomarkers

Pretegiani E, Garces P, Antoniades CA, Sobanska A, Kovacs N, Ying SH, Gupta AS, Perlman S, Szmulewicz DJ, Pane C, Németh AH, Jardim LB, Coarelli G, Kuzmiak M, Milovanovic A, Traschütz A, Tarnutzer AA. Best Oculomotor Endpoints for Clinical Trials in Hereditary Ataxias: A Systematic Review and Consensus by the Ataxia Global Initiative Working Group on Digital‑Motor Biomarkers. Cerebellum. 2025 Aug 13;24(5):141. doi: 10.1007/s12311-025-01894-z. PMID: 40801974; PMCID: PMC12350468. 

Through a systematic MEDLINE search we identified 130 articles reporting oculomotor/vestibular recordings in patients with HCAs. A total of 2,018 subjects were included: 1,776 with genetically-confirmed and 242 with clinically-defined HCAs. Studied diseases included spinocerebellar ataxias (SCA) 1/2/3/6/7/27B, episodic ataxia type 2, Friedreich ataxia, RFC1-related ataxia, fragile X-associated tremor/ataxia syndrome, cerebrotendinous xanthomatosis, ataxia-telangiectasia, ataxia with oculomotor apraxia types 1&2, and Niemann-Pick disease type C.

FRIEDREICH ATAXIA- STEROIDOGENESIS (FRIEDSTERO)

ClinicalTrials.gov ID NCT07123142.

Sponsor Istanbul University

Information provided by Ozge Bayrak Demirel, Istanbul University (Responsible Party) Last Update Posted 2025-08-14 

Friedreich's ataxia (FA) is a rare autosomal recessive disorder caused by GAA repeat expansion in the FXN gene, leading to impaired iron-sulfur (Fe-S) cluster biosynthesis and mitochondrial dysfunction. Fe-S clusters are essential for the function of several enzymes involved in steroid hormone production. While animal and cell culture studies suggest impaired steroidogenesis in FA, no clinical study has systematically evaluated this in human patients. This pilot study aims to investigate adrenal and gonadal steroidogenesis pathways in FA patients using LC-MS/MS-based steroid profiling. A total of 11 genetically confirmed FA patients followed at Istanbul Faculty of Medicine will be enrolled. Clinical data and serum samples will be collected and compared with those of 15 age- and sex-matched healthy controls. The findings are expected to enhance understanding of endocrine alterations in FA and guide future therapeutic approaches.

Larimar Therapeutics Reports Second Quarter 2025 Financial Results

BALA CYNWYD, Pa., Aug. 14, 2025 (GLOBE NEWSWIRE) -- Larimar Therapeutics, Inc. (Larimar). Initial data from the 50 mg dose in the open label study and the adolescent PK run-in study planned for program update in September 2025 

Adolescent participants from the PK run-in study and patients with FA who have not participated in prior nomlabofusp clinical studies are currently screening and enrolling in the open label study; planning to enroll children (2 to 11 years of age) directly into the open label study

FDA recommended that the safety database include at least 30 participants with continuous study drug exposure for 6 months, and a subset of at least 10 participants for 1-year; large majority of safety data should be from participants receiving 50 mg nomlabofusp

Published two peer-reviewed articles; the nonclinical data included in the publications were part of the data submitted to FDA to support the mechanism of action of nomlabofusp and the potential use of skin FXN concentrations as a reasonably likely surrogate endpoint 

BLA seeking accelerated approval on track to be submitted in the second quarter of 2026 

Global Phase 3 study activities ongoing including qualification of identified sites with patient recruitment expected to initiate later this year.

Lexeo Therapeutics Reports Second Quarter 2025 Financial Results and Operational Highlights

NEW YORK, Aug. 14, 2025 (GLOBE NEWSWIRE) -- Lexeo Therapeutics, Inc.​. Breakthrough Therapy designation granted for LX2006 based on interim data from Phase I/II trials demonstrating clinically meaningful improvements in cardiac and neurologic measures of Friedreich ataxia 

LX2006 selected for FDA Chemistry, Manufacturing, and Controls Development and Readiness Pilot (CDRP) program, created to facilitate CMC registrational readiness and support faster patient access. Eight participants dosed in Phase I/II clinical trial (HEROIC-PKP2) of LX2020 for PKP2-ACM; interim clinical data update on track for second half of 2025

Solid Biosciences Inc. Reports Progress in Clinical Trials and Financial Highlights for Q2 2025

Quiver Quantitative. Aug. 12, 2025

SGT-212 for Friedreich’s Ataxia (FA) The Company expects to initiate a first-in-human, open-label, Phase 1b clinical trial of SGT-212 in the fourth quarter of 2025. 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 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.

Manejo anestésico de tempestade tireoidiana em paciente com ataxia de Friederich. Relato de caso

Giovanna Calixto Rossi Marques de Souza, Laura Faleiros de Lima, Paula Ariane Toneli Reis. Archives of Health, Curitiba, v.6, n.4, special edition, p.01-06, 2025. ISSN 2675-4711 DOI:10.46919/archv6n4espec-15350 

Este artigo apresenta o relato de um caso clínico de paciente com ataxia de Friedreich submetido a procedimento de emergência em meio a uma crise tireotóxica, e realiza uma revisão sistemática da literatura sobre as condutas anestésicas mais adequadas. Utilizando as bases de dados SciELO, LILACS e BVS, foram selecionados artigos brasileiros dos últimos 15 anos que abordam tempestade tireoidiana, ataxia de Friedreich e anestesia. O objetivo foi avaliar abordagens seguras e eficazes na anestesia para pacientes com essas condições associadas. A análise dos dados revelou que o uso de agentes anestésicos cardioestáveis, o controle rigoroso do estado hemodinâmico e metabólico, e a vigilância contínua no pós-operatório são imprescindíveis. 

 

Clinical and cognitive assessment in Friedreich ataxia clinical trials: a review

Darriba Á, Munnich A, Cardoso-Leite P, Funalot B, Waszak F. Clinical and cognitive assessment in Friedreich ataxia clinical trials: a review. Front Neurol. 2025 May 22;16:1558493. doi: 10.3389/fneur.2025.1558493. PMID: 40488204; PMCID: PMC12142069.

We argue for the inclusion of cognitive and speech-related assessments in clinical trials, and examine the potential of developments in cognitive neuroscience and technology to address current measurement challenges and support more accurate and comprehensive evaluation of treatment effects. These innovations have the potential to complement existing approaches, enhance trial design, and advance clinical care.

Efficacy of Omaveloxolone Treatment for Dysphagia in French Patients With Friedreich's Ataxia

Conditions: Friedreich Ataxia Interventions: Drug: SKYCLARYS (omaveloxolone) Sponsors: Centre Hospitalier Universitaire de Nice 

Not yet recruiting 

Last Update Posted 2025-06-10 

This study aimed to comprehensively evaluate the effect of Omaveloxolone on dysphagia after six months of treatment, in a cohort of French patients with Friedreich's ataxia who benefited from early access to treatment between February 2024 and May 2025. The severity of dysphagia will be assessed using the Sydney Swallow Questionnaire (SSQ), completed by patients at baseline and after six months of Omaveloxolone treatment.

Increase of Plasma Biomarkers in Friedreich's Ataxia: Potential Insights into Disease Pathology

Rummey C, Thomas-Black G, Garcia-Moreno H, Lynch DR, Abeti R, Arisoy H, Heslegrave A, Zetterberg H, Giunti P; European Friedreich's Ataxia Consortium for Translational Studies (EFACTS). Increase of Plasma Biomarkers in Friedreich's Ataxia: Potential Insights into Disease Pathology. Mov Disord. 2025 Jun 11. doi: 10.1002/mds.30250. Epub ahead of print. PMID: 40498047. 

NfL is a sensitive biomarker in early FRDA but decreases with age, converging with control values after 35-40 years. This age-dependent pattern must be considered when interpreting the effect of interventions in clinical trials. Especially in younger (age < 10 years) or presymptomatic patients and control subjects, additional longitudinal sampling is warranted. Elevated tau levels suggest involvement in underlying disease pathophysiology.

Characteristics of Adverse Events and Clinical Risks of Omaveloxolone Based on FAERS Data

Liu H, Fan D, Tao H, Shen Z, Yao K. Characteristics of Adverse Events and Clinical Risks of Omaveloxolone Based on FAERS Data. Cerebellum. 2025 Jun 18;24(4):119. doi: 10.1007/s12311-025-01873-4. PMID: 40533692. 

This study aims to evaluate post-marketing adverse events (AEs) associated with its clinical use by analyzing data from the FDA Adverse Event Reporting System (FAERS). We collected all adverse reaction reports associated with omaveloxolone from the first quarter of 2023 (Q1 2023) to the fourth quarter of 2024 (Q4 2024) in the FAERS database and performed signal detection using four distinct pharmacovigilance methods: the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM).

Salutary Effects of Overexpression of Rsm22, an Assembly Factor for the Mitochondrial Ribosome, on Frataxin/Yfh1 Depletion Phenotypes in Saccharomyces cerevisiae

Pandey AK, Singh P, Pain J, Dancis A, Pain D. Salutary Effects of Overexpression of Rsm22, an Assembly Factor for the Mitochondrial Ribosome, on Frataxin/Yfh1 Depletion Phenotypes in Saccharomyces cerevisiae. Biomolecules. 2025 May 28;15(6):785. doi: 10.3390/biom15060785. PMID: 40563426; PMCID: PMC12191369. 

Here, we describe frataxin/Yfh1 bypass by overexpression of Rsm22, an assembly factor for the mitochondrial ribosome. Rsm22 overexpression in Yfh1-depleted yeast cells restored critical processes in mitochondria, including Fe-S cluster assembly, lipoic acid synthesis, iron homeostasis, and heme synthesis, to a significant extent. Formation of cytoplasmic Fe-S proteins was also restored, suggesting recovery of the mitochondrial ability to generate the (Fe-S)int intermediate that is exported from mitochondria and is utilized for cytoplasmic Fe-S cluster assembly. Importantly, an essential component of the mitochondrial iron-sulfur cluster machinery, namely ferredoxin, was virtually absent in mitochondria lacking Yfh1, but it was recovered with Rsm22 overexpression. Interestingly, ferredoxin overexpression could offset some of the effects of Yfh1 depletion. Ferredoxin has recently been shown to bind to the cysteine desulfurase protein Nfs1 at the same site as Yfh1, in a conserved arginine patch on Nfs1, such that ferredoxin binding at this site may confer frataxin-bypass activity.

Friedreich's ataxia: A case series, literature review, and recommendations for pregnancy

Dakin A, Bogdanova-Mihaylova P, Walsh RA, Murphy SM, Ward D, Maher N, McCarthy CM. Friedreich's ataxia: A case series, literature review, and recommendations for pregnancy. Int J Gynaecol Obstet. 2025 Jul 13. doi: 10.1002/ijgo.70361. Epub ahead of print. PMID: 40653762. 

Pregnancies complicated by chronic health conditions, such as FRDA, can pose clinical, logistical, and organizational challenges to optimize management and outcomes. We delineate the management challenges posed in the management of the largest Irish case series of pregnant patients with FRDA and extrapolate recommendations that can be applied to clinical practice through a literature review.

The Use of Assistive Gait Devices Can Reduce the Risk of Falls in Patients With Neuromuscular Diseases Following a Training Period.

Conditions: Inclusion Body Myositis; Myotonic Dystrophy 1; Myotonic Dystrophy 2; Facio-Scapulo-Humeral Dystrophy; Limb Girdle Muscular Dystrophies; Pompe Disease (Infantile-Onset); Myasthaenia Gravis; Lambert Eaton (LEMS); Spinal Muscular Atrophy (SMA); Guillain Barré Syndrome; Chronic Inflammatory Demyelinating Polyneuropathy; Friedreich Ataxia; Hereditary Motor and Sensory Neuropathies Interventions: Device: Assistive gait devices combined with physiotherapy Sponsors: LMU Klinikum 

Enrolling by invitation 

Last Update Posted 2025-07-18

The planned project is an intervention study to assess the risk of falling after adaptation of an assistive gait devices in patients with the following neuromuscular diseases: Inclusion body myositis, myotonic dystrophy, limb girdle and facioscapulohumeral muscular dystrophies, Pompe disease, Lambert-Eaton syndrome, myasthenia gravis, spinal muscular atrophy, Guillain-Barré syndrome, chronic inflammatory demyelinating polyradiculoneuropathy, Friedreich's ataxia and hereditary motor and sensory neuropathy

STRUCTURAL VALIDITY AND INTER-RATER RELIABILITY OF THE ATAXIA TRUNK, LOWER AND UPPER EXTREMITY SCALE (ATLAS) (ATLAS ReVA)

Conditions: Ataxia, Cerebellar; Ataxia, Gait; Ataxia, Motor; Ataxia; Ataxia, Spinocerebellar; Ataxias, Hereditary; Ataxia - Other Interventions: Other: New Scale to evaluate ataxia motor symptoms Sponsors: Haute Ecole de Santé Vaud 

Not yet recruiting 

Last Update Posted 2025-07-23

Ataxia is a neurological disorder affecting coordination, caused by damage to the cerebellum, brainstem, or related pathways. It can be hereditary (e.g., Friedreich's ataxia) or acquired (e.g., multiple sclerosis, stroke). Though rare, ataxia significantly impacts quality of life and independence. Treatments are limited and mainly focus on multidisciplinary rehabilitation. Accurate assessment is essential, yet current tools like Scale for the Assessment and Rating of Ataxia (SARA) have limitations. This study aims to validate a new scale, named the Ataxia Trunk, Lower And upper extremity Scale (ATLAS), through Rasch analysis, to develop a shorter, reliable version. It will assess internal consistency, construct validity, and inter-rater reliability

Electroencephalogram in Patients With Friedreich's Ataxia for the Study of the Structural and Functional Connectome. (CONNETTOMA)

Conditions: Friedreich's Ataxia; Motor Disorders Interventions: Device: HD-EEG recordings, combined with cognitive and motor assessment Sponsors: IRCCS Eugenio Medea 

Recruiting 

Prospective, exploratory, multicenter pilot study investigating the structural and functional connectome in patients with Friedreich's Ataxia (FRDA) using high-density electroencephalogram (HD-EEG). The aim is to identify neurophysiological biomarkers and analyze the relationship between cortical connectivity, cognitive functioning, and clinical severity, particularly in response to rehabilitation treatment.

Design Therapeutics Highlights Progress Across Lead GeneTAC® Programs and Reports Second Quarter 2025 Financial Results

CARLSBAD, Calif., Aug. 07, 2025 (GLOBE NEWSWIRE) -- Design Therapeutics, Inc.

Friedreich Ataxia (FA):

Today, Design announced early pharmacokinetics (PK) data for DT-216P2 demonstrating favorable translation from NHPs to humans with both intravenous (IV) and subcutaneous (SC) administration and an improved product profile compared to the prior DT-216 formulation (DT-216P1). 

Human plasma PK profiles of DT-216P2 were consistent with NHP data following both IV and SC single-dose administration. 

DT-216P2 exhibited improved exposure and PK parameters compared to DT-216P1, including higher AUC and sustained plasma levels at comparable doses. 

DT-216P2 has been generally well-tolerated, and based on clinical and non-clinical data, Design believes the injection site thrombophlebitis seen with DT-216P1 is no longer an issue limiting continued development of DT-216. 

In June, Design announced that it had received a clinical hold notice from the U.S. Food and Drug Administration (FDA) regarding its Investigational New Drug (IND) application for DT-216P2. FDA’s request pertains to the starting dose in the U.S., which the company plans to address with clinical data and, if needed, nonclinical data, in order to initiate studies for DT-216P2 in the U.S. Design continues to dose patients in its RESTORE-FA Phase 1/2 MAD trial of DT-216P2 outside the U.S. 

 

The Tiger Milk Medicinal Mushroom Lignosus rhinocerus (Agaricomycetes) Mitigates Oxidative Damage in a Cellular Model Mimicking Friedreich's Ataxia

Phang MWL, Hisam NSM, Supandi F, Cheng PG, Lim SH, Lim LW, Wong KH. The Tiger Milk Medicinal Mushroom Lignosus rhinocerus (Agaricomycetes) Mitigates Oxidative Damage in a Cellular Model Mimicking Friedreich's Ataxia. Int J Med Mushrooms. 2025;27(11):63-87.  doi: 10.1615/IntJMedMushrooms.2025059734. PMID: 40752029. 

The Tiger Milk Medicinal Mushroom Lignosus rhinocerus (Agaricomycetes) Mitigates Oxidative Damage in a Cellular Model Mimicking Friedreich's Ataxia. We evaluated the protective effects of L. rhinocerus ethanol fraction (LREF) in Friedreich's ataxia (FRDA) by using fibroblasts treated with L-buthionine sulfoximine (L-BSO) to induce oxidative damage to mimic the pathogenesis of the disease.

Muscle Endurance Training in a Person with Friedreich's Ataxia

McGarrell NT, Green ME, McCully KK. Muscle Endurance Training in a Person with Friedreich's Ataxia. Muscles. 2025 Jan 9;4(1):1. doi: 10.3390/muscles4010001. PMID: 40757576; PMCID: PMC12121318.

Friedreich's ataxia (FRDA) results from a faulty mitochondrial protein known as Frataxin. The purpose of this case report was to test whether skeletal muscle in FRDA can adapt to an endurance-based training program using neuromuscular electrical stimulation (NMES)Muscle adaptations to endurance training were seen in FRDA, but increased training might be needed to test if mitochondrial capacity can improve. 

Hypertrophic cardiomyopathy with ataxic gait: a cardiac clue to a neurologic diagnosis

Saha S, Jha A, Yadaw M, Tiwari B. Hypertrophic cardiomyopathy with ataxic gait: a cardiac clue to a neurologic diagnosis. BMJ Case Rep. 2025 Aug 4;18(8):e265662. doi: 10.1136/bcr-2025-265662. PMID: 40759502. 

 

In this case report, we describe a case of non-sarcomeric paediatric HCM associated with mitochondrial disorder (Friedreich's ataxia). Friedreich's ataxia is a neurodegenerative disorder caused by a homozygous GAA triplet repeat expansion in the Frataxin gene. Symptoms include progressive ataxia, dysarthria, peripheral neuropathy and diabetes mellitus. Cardiovascular involvement, often presenting as HCM, emerges during adolescence and affects nearly two-thirds of patients. This case also highlights the importance of genetic analysis in paediatric cardiomyopathies. 

 

Fusion proteins attract funds and biopharma partnerships

August 6, 2025. Labiotech.eu. Fusion proteins have long been on the market to treat several diseases, including cancer, autoimmune, and rare conditions. These therapeutic agents have caught the attention of biopharma and investors alike these past months attracting dollars from deep pockets in the pursuit of commercial success. Nomlabofusp developer Larimar Therapeutics $69 million public offering.

Conditions of CDA’s recommendations

Canadian Journal of Health Technologies. July 2025 Volume 5 Issue 7. Reimbursement Recommendation: Omaveloxolone (Skyclarys).Indication: For the treatment of Friedreich’s ataxia in patients 16 years of age and older. 

Sponsor: Biogen Canada Inc. 

Final recommendation: Reimburse with conditions Canada’s Drug Agency (CDA-AMC) is a pan-Canadian health organization. Canada’s Drug Agency (CDA-AMC) recommends that Skyclarys be reimbursed by public drug plans for the treatment of Friedreich’s ataxia (FA) if certain conditions are met. 

Based on the sponsor’s submission, omaveloxolone-SOC is not cost-effective at a WTP of $50,000 per QALY gained when either the public health care payer or a societal perspective is adopted. Price reductions of 95% to 97% would be required for omaveloxolone-SOC to be cost-effective compared to SOC from the societal and public payer perspectives, respectively, at this threshold.

 

In vivo applications and toxicities of AAV-based gene therapies in rare diseases

Zhao, Q., Peng, H., Ma, Y. et al. In vivo applications and toxicities of AAV-based gene therapies in rare diseases. Orphanet J Rare Dis 20, 368 (2025). doi:10.1186/s13023-025-03893-z 

As of early 2024, only eight AAV-based gene therapy drugs have been approved.AAV-based gene therapies have revolutionized treatment for rare diseases; however, addressing toxicity and improving long-term efficacy remain key challenges.

 

First treatment option SKYCLARYS™ (omaveloxolone) for Australians diagnosed with ‘neurogenerative disease’ Friedreich ataxia1

Sydney, Australia – 21st July 2025 – Biogen Australia welcomes the TGA (Therapeutic Goods Administration) approval of SKYCLARYS™ (omaveloxolone) as the first treatment for adults and adolescents aged 16 years and older with the rare, genetic, progressive disease Friedreich ataxia (FA).

SKYCLARYS is not listed on the Pharmaceutical Benefits Scheme (PBS). 

Disease Progression in Children With Friedreich Ataxia: Functional Performance and Other Outcome Assessments in the FACHILD Study

Rummey C, Perlman S, Subramony SH, Corti M, Farmer J, Lynch DR. Disease Progression in Children With Friedreich Ataxia: Functional Performance and Other Outcome Assessments in the FACHILD Study. J Child Neurol. 2025 Jul 24:8830738251353475. doi: 10.1177/08830738251353475. Epub ahead of print. PMID: 40708339; PMCID: PMC12313166.

The FACHILD natural history study aimed to expand knowledge about the disease course and evaluate clinical outcome assessments in children. We report on functional performance testing, clinical rating scales, and patient-reported outcomes as clinical outcome assessments for Friedreich ataxia. Over a 3-year period, all tests and assessments were conducted to evaluate their sensitivity to progression and correlate with established measures such as neurologic rating scales. 

 Disease Progression in Children With Friedreich Ataxia: Functional Performance and Other Outcome Assessments in the FACHILD Study

Evaluation of Mitochondrial Complex 1 Density with [18F]BCPP-EF in a Murine Model and Individuals with Friedreich Ataxia

Evaluation of Mitochondrial Complex 1 Density with [18F]BCPP-EF in a Murine Model and Individuals with Friedreich Ataxia. Laigao Chen, Gaia Rizzo, Christine Bulawa, Koene R.A. Van Dijk, Erica C. Henning, Alain Martelli, Jeffrey Palmer, Avery McIntosh, Marko Pregel, Pengling Sun, Emmanuel Adewunmi, Mark Aldridge, Jackson Chan, Roger N. Gunn, Mickael Huiban, Allan Listanco, Peter T. Loudon, Sara Moz, Jan Passchier, Lauren Sauvage, Rachel Stewart, Lisa Wells, Eugenii A. Rabiner, Lawrence R. Charnas, Richard J. Festenstein, Journal of Nuclear Medicine Jul 2025, jnumed.124.268698; DOI: 10.2967/jnumed.124.268698 

 

Loss of frataxin impacts mitochondrial complex 1 (MC1) activity, suggesting MC1 may be a potential biomarker of frataxin levels and function. Biomarkers evaluated by noninvasive techniques are needed to monitor disease progression and treatment effects in people with Friedreich ataxia. MC1 density as measured using [18F]BCPP-EF–based PET may be a viable biomarker of mitochondrial deficit and frataxin levels in people with Friedreich ataxia.

SFDA Approves Registration Of Skyclarys For Treating Friedreich’s Ataxia In Adults And Adolescents

By OneArabia, Wednesday, July 23, 2025. The Saudi Food and Drug Authority (SFDA) has given the green light for Skyclarys (Omaveloxolone), a drug previously recognised as an orphan drug under their Orphan Drug Program. This medication is designed to treat Friedreich’s ataxia in individuals aged 16 and older.

CDA Issues Positive Reimbursement Recommendation for SKYCLARYS™ (omaveloxolone), the Only Health Canada-Approved Treatment for Managing Friedreich Ataxia

CNW Group Tue, July 29, 2025. TORONTO, July 29, 2025 /CNW/ - Biogen Canada Inc. is pleased to announce a significant step forward for Canadians living with Friedreich ataxia (FA), with the positive reimbursement recommendation by Canada's Drug Agency (CDA) Canadian Drug Expert Committee (CDEC) for SKYCLARYS™ (omaveloxolone) as a treatment for patients 16 years of age and older who meet certain criteria.1 This milestone brings Canadians outside Quebec affected by this rare neurodegenerative disease a step closer to accessing the only approved therapy for the condition.

Solid Biosciences’ SWOT analysis: gene therapy stock poised for growth amid challenges

Investing.com. Published 07/29/2025 

SGT-212 for Friedreich’s Ataxia: Recently received FDA Investigational New Drug (IND) clearance Unique dual-route administration approach targeting both neurologic and cardiac manifestations Phase 1b dose-finding study set to begin in the second half of 2025

RWD132 Onset of Cardiomyopathy and Cardiovascular Disease-Related Burden in Friedreich Ataxia: Real-World Data From Medical Claims

Sheng-Han Kuo, Boyang Bian, Sarah M. England, Daniel R.J. Gomes, Jim McKay, Tony Wang, Robin L. Avila, Susan Perlman, RWD132 Onset of Cardiomyopathy and Cardiovascular Disease-Related Burden in Friedreich Ataxia: Real-World Data From Medical Claims, Value in Health, Volume 28, Issue 6, Supplement 1, 2025, Page S386, ISSN 1098-3015, doi:10.1016/j.jval.2025.04.1715. 

These data show the natural progression of CV events in FA. Our findings demonstrate that patient burden related to progressive CM begins at an early age and that other cardiac disease, particularly arrhythmias and rhythm and heart valve disorders, may begin 2-11 years prior to CM, with CV onset as early as age 7 in the youngest patients. These data have limitations in older populations and those in Medicare but provide previously unavailable data on the onset of CM and CV disease in patients.

False Beliefs, True Deficits: Investigating Social Cognition in Friedreich Ataxia

Heleven E, Vyhnalek M, Karamazovová S, Van Overwalle F, Naeije G. False Beliefs, True Deficits: Investigating Social Cognition in Friedreich Ataxia. Cerebellum. 2025 Jul 11;24(5):128. doi: 10.1007/s12311-025-01886-z. PMID: 40643773. 

 Friedreich ataxia (FA) is a cerebellar neurodegenerative disease primarily known for its motor symptoms, but emerging evidence suggests it also affects higher-order cognitive functions, including Theory of Mind (ToM). This study aimed to assess ToM in individuals with FA using a Picture Sequencing Task (PST) that distinguishes between mechanical, social script, true belief, and false belief scenarios, with a focus on the latter as key marker of mentalizing in cerebellar diseases. 

Our results reveal a selective impairment in false belief reasoning in FA, consistent with ToM deficits observed in other cerebellar and neurodevelopmental disorders.

Unveiling the Idiographic Portrait of Friedreich's Ataxia in an Omani Patient: A Multidisciplinary Case Stud

Al-Adawi, Samir and Al Busaidi, Saoud Jaber and Al Jahwari, Nasra Ali and Rajeev, Neeraja and Alriyami, Maha and ALBusaidi, Alya and Al Kindi, Farah Ahmed and Otaify, Ghada Ahmed and Ambusaidi, Aamal and Al Azri, Faisal Hamad and Gujjar, Arunodaya R. and Bolourkesh, Helia, Unveiling the Idiographic Portrait of Friedreich's Ataxia in an Omani Patient: A Multidisciplinary Case Study. doi:10.2139/ssrn.5344239

Friedreich’s ataxia (FA), a rare inherited disorder that mainly affects Caucasian populations, presents significant diagnostic challenges in regions with diverse genetic backgrounds. This case report details the diagnostic journey of a 22-year-old Omani male with undiagnosed FA, highlighting the value of the idiographic approach within a biopsychosocial framework. Initially presenting with psychotic symptoms, the patient underwent a comprehensive interdisciplinary evaluation, revealing neurological and psychiatric manifestations.

Larimar Therapeutics Publishes Nonclinical Data Supporting the Therapeutic Potential of Nomlabofusp in Patients with Friedreich’s Ataxia

BALA CYNWYD, Pa., July 08, 2025 (GLOBE NEWSWIRE) -- Larimar Therapeutics, Inc. (Larimar) (Nasdaq: LRMR), a clinical-stage biotechnology company focused on developing treatments for complex rare diseases, today announced the publication of two peer-reviewed articles highlighting nonclinical data on the therapeutic potential, pharmacology, and mechanism of action of nomlabofusp as a novel frataxin (FXN) protein replacement therapy designed to address the underlying cause of Friedreich’s ataxia (FA). These data were included in the briefing package reviewed by the U.S. Food and Drug Administration (FDA) in support of potentially using skin FXN concentrations as a reasonably likely surrogate endpoint (RLSE) for Larimar’s registrational program seeking accelerated approval for nomlabofusp.

LEXEO THERAPEUTICS ANNOUNCES FDA BREAKTHROUGH THERAPY DESIGNATION FOR LX2006 IN FRIEDREICH ATAXIA

NEW YORK, July 07, 2025 (GLOBE NEWSWIRE) -- Lexeo Therapeutics, Inc. (Nasdaq: LXEO), a clinical stage genetic medicine company dedicated to pioneering novel treatments for cardiovascular diseases, today announced that the U.S. Food and Drug administration (FDA) has granted Breakthrough Therapy designation to LX2006 based on clinical evidence generated on both cardiac and neurologic measures of Friedreich ataxia (FA). LX2006 has also been selected to participate in the FDA Chemistry, Manufacturing, and Controls (CMC) Development and Readiness Pilot (CDRP) program, intended to enable earlier patient access to therapies with expedited clinical development timelines.

Lexeo Therapeutics Announces FDA Breakthrough Therapy Designation for LX2006 in Friedreich Ataxia

07/07/2025 ;Lexeo Therapeutics (Nasdaq: LXEO) has achieved a significant milestone as its drug candidate LX2006 received FDA Breakthrough Therapy designation for treating Friedreich ataxia (FA). The designation was based on promising interim clinical data from Phase I/II trials showing meaningful improvements in cardiac biomarkers and functional measures. The drug has demonstrated clinically significant improvements in cardiac and neurologic functional measures, with increased frataxin expression observed in all cardiac biopsy participants at three months post-treatment. To date, 17 participants have been treated across two trials. The company plans to initiate a registrational study by early 2026. Additionally, LX2006 has been selected for the FDA's Chemistry, Manufacturing, and Controls Development and Readiness Pilot (CDRP) program, aimed at facilitating faster patient access to promising therapies.

Antisense oligonucleotide therapy for Friedreich’s ataxia patients carrying the c.165+5G>C splicing mutation

Antisense oligonucleotide therapy for Friedreich’s ataxia patients carrying the c.165+5G>C splicing mutation. Yameogo, Pouiré et al. Molecular Therapy Nucleic Acids, Volume 0, Issue 0, 102617. DOI:10.1016/j.omtn.2025.102617

This ASO strategy may be therapeutically feasible for FRDA patients with other point mutations that cause splicing defects. Success in developing treatments for disorders with only a few known cases will give hope to FRDA patients carrying these rare point mutations.

Antisense oligonucleotide therapy for Friedreich’s ataxia patients carrying the c.165+5G>C splicing mutation

Biogen Launches Phase 3 Pediatric Trial Of Omaveloxolone For Friedreich Ataxia

Biogen Inc.June 23, 2025. It has begun dosing in the global Phase 3 BRAVE trial to test omaveloxolone (SKYCLARYS®) in children aged 2 to 16 with Friedreich ataxia (FA), a rare neurological illness. About 255 participants will be included in the randomized, double-blind experiment, which will have a 52-week treatment duration and an open-label extension. SKYCLARYS is now the only approved therapy for FA in people aged 16 and up, and it is available in more than 40 countries.

The primary endpoint of the BRAVE research is the Upright Stability Score, which is part of the modified FA rating scale and is used to assess progression in children. Global enrollment is still ongoing.

The clinical burden of Friedreich ataxia in the United States: A retrospective claims database analysis

The clinical burden of Friedreich ataxia in the United States: A retrospective claims database analysis, Perlman, Susan et al.. Journal of the Neurological Sciences, Volume 0, Issue 0, 123594. doi:10.1016/j.jns.2025.123594

 After matching, the study included 652 patients with FRDA and 3260 matched controls (mean age 33.2 years; 51.4 % females). During the follow-up period (median 26.2 months for cases and 28.3 months for controls), the incremental clinical burden in FRDA cases vs. matched controls was high: patients with FRDA had significantly higher odds of loss of ambulation (odds ratio: 158.0 [95 % confidence interval (CI): 112.4–222.3]), cardiomyopathy (59.2 [41.6–84.1]), scoliosis (49.0 [35.4–67.9]), falls (7.4 [5.9–9.2]), diabetes (2.5 [2.0–3.2]), head injury (2.4 [1.9–3.0]), and fracture (3.3 [2.6–4.2]) compared to controls (all p < 0.001). Patients with FRDA also experienced a higher risk of mortality than controls (hazard ratio: 3.9 [95 % CI: 2.4–6.4]).

Stable Isotope Labeling in Bacteria Enables Characterization and Quantification of Frataxin Protein in a Friedreich’s Ataxia Zebrafish Model

Stable Isotope Labeling in Bacteria Enables Characterization and Quantification of Frataxin Protein in a Friedreich’s Ataxia Zebrafish Model, Teerapat Rojsajjakul, Wonwook Do, Robert B. Wilson, and Ian A. Blair Analytical Chemistry Article ASAP DOI: 10.1021/acs.analchem.4c07095

We developed an alternative strategy involving the use of a stable isotope-labeled internal standard coupled with analysis by high-sensitivity ultrahigh-performance liquid chromatography-multiple reaction monitoring-mass spectrometry (UHPLC-MRM/MS). UHPLC-MRM/MS with a SILIB internal standard was the only way to validate zebrafish heterozygous for a knockout mutation in zFXN as a model for FRDA, illustrating its utility for the characterization and quantification of very low abundance tissue proteins.

Pharmacokinetics and Pharmacodynamics of Nomlabofusp in Non-clinical Studies of Friedreich's Ataxia

De Toni F, Ragaglia V, Schecter D, Miller AS, Gonzalez E, Wagner EJ, Xu X, Payne RM, Mess JN, Baile MG, Clements-Egan A, Shankar G. Pharmacokinetics and Pharmacodynamics of Nomlabofusp in Non-clinical Studies of Friedreich's Ataxia. AAPS J. 2025 Jun 25;27(5):112. doi: 10.1208/s12248-025-01093-y. PMID: 40562976. 

We demonstrate that subcutaneous administration of nomlabofusp distributes in a dose-dependent manner to several organs including the dorsal root ganglion, heart, and skeletal muscle, which are known to be predominantly affected in Friedreich's ataxia, as well as to other tissues, including skin. Plasma nomlabofusp concentrations correlated with levels of human frataxin delivered by nomlabofusp into tissues, and the increases in frataxin were correlated amongst tissues, especially with skin. In the knockout mice, we show that the pharmacokinetics and processing of nomlabofusp were comparable with wild type animals and that treatment with nomlabofusp halts the progression of cardiac dysfunction and significantly increased survival. Together, the findings from these non-clinical studies demonstrate that nomlabofusp exposure increases human frataxin in Friedreich's ataxia-relevant tissues and provide evidence of pharmacologic effects.

Larimar Therapeutics Announces FDA Recommendations on Safety Database, and Other Details of Nomlabofusp BLA Submission for Friedreich’s Ataxia Program

BALA CYNWYD, Pa., June 23, 2025 (GLOBE NEWSWIRE) -- Larimar Therapeutics, Inc. (Larimar) (Nasdaq: LRMR), a clinical-stage biotechnology company focused on developing treatments for complex rare diseases, today announced FDA safety database recommendations and refined timeline for Biologics License Application (BLA) submission to allow for the inclusion of the recommended safety data from adults and children with Friedreich’s Ataxia (FA). This comes following written responses from the U.S. Food and Drug Administration (FDA) based on discussions under the Support for Clinical Trials Advancing Rare Disease Therapeutics (START) pilot program.

Biogen Disappointed by INESSS Recommendation on SKYCLARYS™ and its Impact on Quebec Patients with Friedreich Ataxia

TORONTO, June 5, 2025 /CNW/ - Biogen Canada Inc. is disappointed by INESSS's recommendation against listing SKYCLARYS™ (omaveloxolone), despite its therapeutic potential for individuals living with Friedreich ataxia (FA) — a community in urgent need of treatment options.

Autosomal Recessive Cerebellar Ataxias: Translating Genes to Therapies

Fogel, B.L., Klopstock, T., Lynch, D.R., Maltecca, F., Verma, M., Minassian, B.A., Platt, F.M., Gonçalves, D.F., Puccio, H., Roos, A. and Synofzik, M. (2025), Autosomal Recessive Cerebellar Ataxias: Translating Genes to Therapies. Ann Neurol. doi:10.1002/ana.27271 

 Autosomal recessive cerebellar ataxias (ARCAs) represent over 200 clinically heterogeneous genetic conditions involving degeneration of the cerebellum and associated tracts with resultant impairment of balance and coordination. Advancements in genomic testing have enabled rapid identification of the majority of known recessive disorders, shifting research focus to the development of targeted mechanistic treatments addressing underlying physiological pathways. Molecular classification allows recognition of cellular, biochemical, and genetic targets for high-effect precision therapy development. ARCAs represent a significant global health burden, requiring establishment of a robust pathway for novel therapeutic discovery through modification of mechanisms of disease pathogenesis and subsequent clinical trial development.