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.