Neuroimaging Biomarkers for Friedreich Ataxia: A Cross‐Sectional Analysis of the TRACK ‐ FA Study
Year: 2025
Type: article
Abstract: OBJECTIVE: We aimed to quantify differences in the brain and spinal cord between Friedreich ataxia and controls, stratified by age and disease stage, including for the first time in young children. METHODS: TRACK-FA is the largest prospective, longitudinal, multi-modal neuroimaging study in Friedreich ataxia to date. We assessed individuals with Friedreich ataxia and controls, 5 to 42 years, at 7 sites across 4 continents. The 17 imaging primary outcome measures (POMs) were selected from metrics that showed a significant longitudinal change in previous small-scale studies. These included brain and spinal cord morphometry (structural magnetic resonance imaging [MRI]) and microstructure (diffusion MRI); brain iron levels (quantitative susceptibility mapping); and spinal cord biochemistry (magnetic resonance spectroscopy). This study is registered with ClinicalTrials.gov (NCT04349514). RESULTS: Between February 2021 and August 2023, we assessed 169 individuals with Friedreich ataxia and 95 controls. Compared to controls, individuals with Friedreich ataxia had lower volume of dentate nucleus and superior cerebellar peduncles; smaller cross-sectional area of spinal cord; lower fractional anisotropy and higher diffusivity in spinal cord and superior cerebellar peduncles; and lower total N-acetyl-aspartate/myo-inositol ratio in spinal cord. Morphometric differences in spinal cord and superior cerebellar peduncles increased dramatically with age during childhood, with rapid development in controls, but not in Friedreich ataxia. Many imaging POMs showed significant associations with clinical severity. INTERPRETATION: Our findings provide strong imaging evidence of impaired development of spinal cord and superior cerebellar peduncles during childhood in Friedreich ataxia and open the way for the use of neuroimaging biomarkers in clinical trials. ANN NEUROL 2025;98:386-397.
Source: Annals of Neurology
DOI: 10.1002/ana.27237
Authors: Nellie Georgiou‐Karistianis, Louise A. Corben, Eric F. Lock, Helena Bujalka, Isaac Adanyeguh, Manuela Corti, Dinesh K. Deelchand, Martin B. Delatycki, Imis Dogan, Jennifer Farmer, Marcondes C. França, Anthony S. Gabay, William Gaetz, Ian H. Harding, James Joers, Michelle A. Lax, Jiakun Li, David R. Lynch, Thomas H. Mareci, Alberto R. M. Martinez, Massimo Pandolfo, Marina Papoutsi, Richard G. Parker, Kathrin Reetz, Thiago J.R. Rezende, Timothy P. Roberts, Sandro Romanzetti, David A. Rudko, Susmita Saha, Jörg B. Schulz, Sub H. Subramony, Veena G. Supramaniam, Christophe Lenglet, Pierre‐Gilles Henry
Institutions: Monash University, The University of Melbourne, Murdoch Children's Research Institute, University of Minnesota, University of Florida, Victorian Clinical Genetics Services, Forschungszentrum Jülich, Jülich Aachen Research Alliance, RWTH Aachen University, Friedreich's Ataxia Research Alliance, Universidade Estadual de Campinas (UNICAMP), Children's Hospital of Philadelphia, QIMR Berghofer Medical Research Institute, McGill University, University of Florida Health
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,700
OpenAlex ID: W4408761382