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A global perspective on research advances and future challenges in Friedreich ataxia

Nature Reviews Neurology volume 21, pages 204–215 (2025)Cite this article

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Abstract

Friedreich ataxia (FRDA) is a rare multisystem, life-limiting disease and is the most common early-onset inherited ataxia in populations of European, Arab and Indian descent. In recent years, substantial progress has been made in dissecting the pathogenesis and natural history of FRDA, and several clinical trials have been initiated. A particularly notable recent achievement was the approval of the nuclear factor erythroid 2-related factor 2 activator omaveloxolone as the first disease-specific therapy for FRDA. In light of these developments, we review milestones in FRDA translational and clinical research over the past 10 years, as well as the various therapeutic strategies currently in the pipeline. We also consider the lessons that have been learned from failed trials and other setbacks. We conclude by presenting a global roadmap for future research, as outlined by the recently established Friedreich’s Ataxia Global Clinical Consortium, which covers North and South America, Europe, India, Australia and New Zealand.

Key points

  • Basic and clinical research in Friedreich ataxia (FRDA) has advanced at a fast pace, with milestones being achieved in elucidating the function of frataxin and characterizing the natural history of the disease.

  • The NRF2 activator omaveloxolone was approved as the first specific therapy for FRDA by the FDA in 2023 and the European Commission in 2024.

  • Gene therapies, agents that modulate frataxin gene expression and direct frataxin replacement strategies have also entered clinical trials.

  • The recently formed Friedreich’s Ataxia Global Clinical Consortium (FA GCC) has launched the first global natural history study to harmonize and promote clinical research in FRDA worldwide.

  • The need for more sensitive outcome measures at different stages of the disease and the characterization of cardiac evolution are among the open questions to be addressed by the global consortium.

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Fig. 1: Natural history of Friedreich ataxia.
Fig. 2: Friedreich ataxia pathogenesis and targeted therapeutic approaches.
Fig. 3: Current drug development pipeline in Friedreich ataxia.
Fig. 4: The Friedreich’s Ataxia Global Clinical Consortium.

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Acknowledgements

E.I. and S.B. are members of the European Reference Network for Rare Neurological Diseases (ERN-RND) (project ID 739510).

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Authors and Affiliations

  1. Center for Rare Movement Disorders Innsbruck, Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria

    Elisabetta Indelicato & Sylvia Boesch

  2. Bruce Lefroy Centre for Genetic Health Research, Murdoch Children’s Research Institute, Parkville, Victoria, Australia

    Martin B. Delatycki

  3. Friedreich’s Ataxia Research Alliance, Downingtown, PA, USA

    Jennifer Farmer & Myriam Rai

  4. University of Campinas, Campinas, Brazil

    Marcondes C. França Jr

  5. University of California, Los Angeles, CA, USA

    Susan Perlman

  6. Laboratory of Experimental Neurology, Brussels, Belgium

    Myriam Rai

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  1. Elisabetta Indelicato
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Contributions

E.I. researched data for the article. E.I., J.F., S.P., M.R. and S.B. contributed substantially to discussion of the content. E.I., M.B.D. and M.C.F. wrote the article. All authors reviewed and/or edited the manuscript before submission.

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Indelicato, E., Delatycki, M.B., Farmer, J. et al. A global perspective on research advances and future challenges in Friedreich ataxia. Nat Rev Neurol 21, 204–215 (2025). https://doi.org/10.1038/s41582-025-01065-y

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