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.