3 Blood Biomarkers May Be Used to Monitor Friedreich’s Ataxia Status, Study Suggests

High blood levels of three specific proteins may represent new biomarkers to monitor active immune cells and ongoing nerve cell damage in Friedreich’s ataxia, researchers suggest.

These findings were reported in the study, “Plasma Markers of Neurodegeneration Are Raised in Friedreich’s Ataxia,” published in the journal Frontiers in Cellular Neuroscience.

Friedreich’s ataxia is caused by genetic mutations in the FXN gene leading to faulty mitochondria function and consequent inefficient cellular energy production, mainly affecting nerve cells.

Despite the advances made to better understand the underlying mechanism involved in this disease, there are still no reliable and accurate tools to effectively diagnose and monitor the progression of Friedreich’s ataxia.

To address this issue, researchers at University College London evaluated the diagnostic potential of several blood proteins to monitor Friedreich’s ataxia.

The team focused on the analysis of glial fibrillary acidic protein (GFAP), a biomarker previously linked to the activity of nervous system immune cells (glial cells), as well as of neurofilament-light chain (NfL), total tau (t-tau), and ubiquitin C-terminal hydrolase L1 (UCHL1), three proteins associated with nerve cell damage.

They analyzed blood samples collected from 33 people with confirmed Friedreich’s ataxia and from 13 age- and sex-matched healthy volunteers.

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The patients had experienced disease onset by a median age of 13, with only six patients having late-onset Friedreich’s ataxia (after the age of 25). All patients had clinical manifestations of nerve cell damage (neuropathy) when the samples were collected.

Researchers found that levels of NfL were 2.2 times higher and GFAP 1.7 times higher in Friedreich’s ataxia patients than in controls. Patients also had 2.9 times more CHL1 protein, while t-tau protein levels were similar between the two groups.

Further analysis failed to reveal any association between these proteins levels and disease symptoms severity, as measured by the Scale for the Assessment and Rating of Ataxia (SARA) score, nor with the number of GAA repeats in the FXN gene — a genetic feature linked to disease severity.

“This study represents the first investigation of plasma markers of neurodegeneration in Friedreich’s ataxia,” the researchers wrote. “[Findings] may serve as the basis of further exploration of these brain-derived proteins as promising biomarkers in Friedreich’s ataxia.”

Since each of these proteins is released by different cells, this data provides new evidence on the contribution of immune cells, as well as the progressive damage of different subsets of immune cells, on the development of the disease.

“Future studies are needed to confirm our findings and determine whether, when applied to more heterogeneous cohorts, they serve as useful markers of disease severity,” they said.