Emerging biomarkers for Friedreich’s ataxia

Last updated Sept. 17, 2025, by Lindsey Shapiro, PhD
Medically reviewed by David Lynch, MD, PhD

There is an ongoing need to identify reliable, noninvasive biomarkers to monitor the progression of Friedreich’s ataxia (FA) and therapeutic responses.

Current clinical monitoring tools, such as the modified Friedreich Ataxia Rating Scale, require at least one to two years to demonstrate a disease-modifying effect of an investigational drug and have limited sensitivity. Biomarkers capable of capturing subtle, yet meaningful, treatment benefits may expedite clinical trials and reduce costs associated with drug development.

A wide range of potential biomarkers has been investigated; however, disease complexity and clinical variability complicate the universal application of any single one. Composite biomarkers that integrate clinical, neuroimaging, and biochemical data may prove to be a more sensitive way of tracking FA progression, although validation for such an approach is needed.

Biofluid biomarkers

Various blood-based biomarkers reflective of processes central to the pathophysiology of FA have been evaluated.

Frataxin

A loss of the mitochondrial protein frataxin is the hallmark of FA, and its levels usually correlate with clinical status. An assay to measure the biologically active, mature form of frataxin in blood would be useful for monitoring the effects of disease-modifying therapies, particularly those designed to increase frataxin.

Various analytical approaches have been developed for this purpose, although there are challenges in accurately measuring the correct form of frataxin in bodily fluids, as well as in relevant tissues.

Neurodegeneration markers

Emerging research indicates that some plasma biomarkers of neurodegeneration seen in other disorders, including the neurofilament light chain (NfL), are also elevated in FA.

NfL is likely released in the extracellular space after neuronal injury and can be measured in the cerebrospinal fluid or plasma, where its presence may reflect ongoing neurodegeneration.

NfL may be a promising FA biomarker, although its specific correlation with disease progression and treatment requires further study.

Other biomarkers

Frataxin loss in FA contributes to mitochondrial dysfunction. Biomarkers of mitochondrial impairment, including reductions in components of the electron transport chain complexes, may be useful in monitoring FA.

The long noncoding RNA TUG1 is found to be downregulated in FA, correlating with earlier disease onset and greater disease severity, supporting its potential as an early, noninvasive disease biomarker.

Imaging biomarkers

Structural and diffusion MRI suggest impaired development of the spinal cord and superior cerebellar peduncles during childhood for the FA patient, correlating with scores on clinical scales.

These neuroimaging findings may thus serve as sensitive biomarkers of disease progression in FA, particularly for young children whose clinical scales are less reliable, as the development of the cerebellum and motor systems on them can confound scores.

Left ventricular mass index assessed via cardiac MRI may be a reliable marker for cardiac disease progression in FA, serving to identify patients at risk of severe cardiomyopathy and in need of early intervention. Further evidence is needed from cardiac natural history to ascertain if hypertrophy mirrors the long-term cardiac events in FA.