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.