Study Evaluates Biomarkers in FA for Relevance in Therapeutic Trials

When testing new compounds to treat Friedreich’s ataxia (FA), it is vital to have a metric for determining the efficacy of these compounds. Some studies have suggested using the iron content of dentate nuclei in the cerebellum as a biomarker for determining the efficacy of siderophores and antioxidants in treating FA, but a study from Germany showed that measuring iron content by MRI relaxometry is not sufficient for detecting biomarkers during FA treatment.

In the study, “Cerebellar Pathology in Friedreich’s Ataxia: Atrophied Dentate Nuclei with Normal Iron Content,” 14 age- and gender-matched FA patients with a mean age of 38 years were evaluated against 14 healthy individuals by whole-body MRI using two different scanners at timepoints less than four months apart. Volumetry was used for measuring the volume of the dentate nuclei and the cerebellum. Relaxometry was used to measure the iron content in the cerebellum, left and right dentate nuclei, globus pallidus, and corpus callosum in the brain.

As to be expected, the researchers found a significant difference in the volume of the dentate nuclei between groups: FA patients had smaller volumes than control patients. The same was true for the cerebellum, but not for the cerebrum. However, despite the difference, there was no significant correlation between dentate nuclei volume and clinical ratings scores or symptom duration. Further, there was no correlation between cerebellar volume and clinical rating scores or disease duration.

When the researchers analyzed the results of the relaxometry measurements, they found no significant difference in iron content of the dentate nuclei between FA patients and controls. What’s more, there was no significant correlation between relaxometry rates and clinical ratings scores of patients. The team determined that the two different scanning methods agreed within all structures evaluated, suggesting that the lack of a difference was not a function of error.

While this was the first study to show dentate nuclei atrophy in FA patients using conventional volumetry MRI, the team could not show a difference in iron levels of the dentate nuclei despite previous reports identifying higher iron levels in FA patients. “Age differences in the study populations might explain differences between our findings and the earlier studies,” suggested the authors. “We found that the iron content in the dentate nuclei tended to increase with age in healthy subjects.”

“Our volumetric and relaxometric assessments demonstrate degeneration of the dentate nuclei in the presence of normal dentate iron content,” concluded the authors. “We suggest a cautious handling of relaxation rates as a biomarker in trials concerning FA therapy.”