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.