Uric Acid Levels May Be Biomarker for Friedreich’s Ataxia, Study Suggests

José Lopes, PhD avatar

by José Lopes, PhD |

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uric acid levels as biomarker

Serum uric acid (UA) levels are increased in Friedreich’s ataxia patients and may be a disease biomarker as well as a new therapeutic target, Italian researchers suggests.

Their study, “Serum uric acid in Friedreich Ataxia,” appeared in the journal Clinical Biochemistry.

Friedreich’s ataxia (FA) is a rare inherited disease that affects about one in 50,000 people in the U.S. FA typically begins in childhood. Patients with FA first experience difficulty in walking, which usually leads to needing a wheelchair within 10 years of symptoms onset, and many are completely incapacitated by middle age.

The disorder is caused by abnormal repeats of the GAA sequence of nucleotides (the building blocks of DNA) in the FXN gene. Mutations in FXN lead to reduced production of frataxin, a critical protein for the activity of mitochondria – which provide energy for cells – in the nervous system.

Frataxin regulates iron metabolism, redox homeostasis (the oxidative/nucleophilic balance maintained by redox signaling enzymes), and mitochondrial energy production. As a result, FA patients exhibit greater sensitivity to oxidative damage.

Serum, or blood, uric acid (UA) has antioxidant effects. Its levels are reduced in several neurodegenerative disorders, such as Parkinson’s, Alzheimer’s, frontotemporal dementia, and progressive supranuclear palsy. Blood UA levels reflect clinical features and constitute a biomarker in Parkinson’s.

But there have been no studies exploring serum uric acid levels in Friedreich’s ataxia, researchers said.

The lack of biomarkers predicting disease severity and progression limits clinical advancements and the correct assessment of disease-modifying treatments in ongoing trials.

The researchers compared serum UA levels in 19 Friedreich’s ataxia patients and 26 healthy people to evaluate correlations of clinical parameters and UA levels, as well as its potential as an FA disease biomarker.

Results showed that patients with FA had higher uric acid levels than healthy people, regardless of age, gender, and body mass index. This finding contradicts studies in other neurodegenerative disorders.

“We speculate that such a finding may result from biochemical impairment induced by the genetic [frataxin] defect, acting as a sort of compensatory antioxidant defense,” investigators wrote.

Specifically, previous research suggests that impaired mitochondrial function and oxidative stress lead to increased uric acid levels.

The results did not reveal correlations of UA levels with clinical severity or disease duration, which could be due to the small sample size, the authors observed.

Overall, the increased uric acid levels in FA patients suggest “a potential use as disease diagnostic biomarker, mainly reflecting the underlying oxidative processes, rather than a prognostic predictor,” the researchers stated.

Although further prospective studies are needed with more patients, the authors add that clinical trials should analyze whether frataxin replacement therapy modifies serum UA levels, to better understand the clinical relevance of this potential biomarker.