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.