In Friedreich’s ataxia, neurodegeneration related to dysfunctional iron metabolism has been described in the cerebellum – a brain region crucial for movement coordination. A new study, however, shows that disturbed iron metabolism with resulting tissue damage is far more widespread, and may serve as a biomarker of disease progression or treatment response.
The underlying mutation of Friedreich’s ataxia alters the expression of the protein frataxin. This mitochondrial factor is involved in iron metabolism, and earlier studies have shown that iron tends to accumulate in neuronal nuclei in the cerebellum, leading to cell death.
Considering that other brain structures also have high iron levels, express frataxin, and are involved in movement, researchers at Melbourne, Australia’s Monash University decided to explore whether similar iron-related tissue destruction could be found in other regions of the brain, contributing to Friedreich’s ataxia pathology.
Using MRI, researchers scanned the brains of 30 patients with Friedreich’s ataxia and 33 healthy control individuals.
The study, “Tissue atrophy and elevated iron concentration in the extrapyramidal motor system in Friedreich ataxia: the IMAGE-FRDA study,“ published in the Journal of Neurology, Neurosurgery and Psychiatry, found a high iron content in structures of the midbrain, in addition to the cerebellum. There was also a tendency for an increase in deep structures called basal ganglia. Moreover, the volume of the affected brain structures was lower in Friedreich’s ataxia patients.
In Friedreich’s ataxia, the frataxin gene holds repeats of three DNA bases, and the number of repeats differs between patients. When investigating the iron content in the cerebellum, the team noted that the iron levels reflected both mutation and disease severity. Likewise, the volume of the thalamus – a brain structure working as a connective hub – was lower the more repeats a patient had in their frataxin gene. The volume of several structures could also be linked to the severity of motor symptoms.
These findings indicate that measuring tissue volume of specific structures by MRI might serve as a set of biomarkers that are sensitive to disease expression and progression. Such markers could also be useful for tracking the efficiency of treatment.
Still, the results need to be confirmed in studies following patients over time to cement their value as markers.