MicroRNAs may help detect cardiomyopathy in Friedreich’s ataxia
Two-marker blood test model showed promise in study
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Two microRNAs (miRNAs) — molecules that help regulate gene activity — may serve as biomarkers of cardiomyopathy in people with Friedreich’s ataxia (FA), according to results of a recent study.
Combining the levels of these two miRNAs, called miR-323a-3p and miR-625-3p, into a single predictive model showed strong ability to distinguish FA patients with hypertrophic cardiomyopathy (HCM) from those without it, with a score of about 0.81 on a statistical measure of performance.
“These findings highlight the potential of molecular biomarkers to improve early cardiac detection and individualized monitoring in [FA],” the authors wrote.
The study, “Validation of circulating miR-323a-3p and miR-625-3p to classify hypertrophic cardiomyopathy in Friedreich’s ataxia,” was published in Scientific Reports.
Researchers look for biomarkers of FA heart complications
FA is an inherited disease marked by low production of a protein called frataxin, which is essential for the normal function of mitochondria, the cell’s energy-producing structures. This leads to progressive neurological damage and a loss of muscle control and coordination. Other complications include HCM, a thickening of the heart muscle.
Because FA can progress differently from person to person, there is a need for reliable biomarkers — measurable indicators in the body — to track disease status and provide early warning of specific complications, particularly those associated with HCM.
miRNAs, small molecules that regulate gene expression, or gene activity, have emerged as promising candidates for this role. Changes in the levels of specific miRNAs in the bloodstream have already been linked to both neurodegenerative and cardiovascular diseases, making them particularly relevant to FA.
In previous work, a research team in Spain identified seven microRNAs as potential FA biomarkers. Among them, one, called miR-323-3p, showed promise for identifying FA patients with cardiomyopathy.
To further assess its potential as a cardiomyopathy biomarker, the team collected blood samples from 34 people with FA, half of whom were men. Fifteen (44%) had also been diagnosed with cardiomyopathy, and nine (26%) had diabetes. The study also included 34 healthy individuals who served as controls.
From blood tests, five of the original seven miRNAs were confirmed to be elevated in FA patients compared with controls: miR-323a-3p, miR-128-3p, miR-625-3p, miR-151a-5p, and miR-330-3p.
Among patients with available cardiac data, two miRNAs stood out. miR-323a-3p was higher in FA patients with cardiomyopathy, whereas miR-625-3p was lower.
Two-microRNA model shows promise for HCM classification
In the same cardiac-data subgroup, echocardiographic measurements (ultrasound imaging of the heart) showed that two structural measures of heart wall thickness were significantly greater in patients with HCM, whereas other measurements did not differ statistically between the groups.
The researchers used a statistical tool to assess how well the biomarkers distinguished patients with HCM from those without. When miR-323a-3p and miR-625-3p were combined into a single predictive model, it showed an AUC of about 0.81, a measure of how well a test distinguishes between two groups.
At a specific threshold, this combined model achieved a sensitivity of 72.7% (its ability to correctly identify patients with HCM) and a specificity of 71.4% (its ability to correctly rule out HCM).
In addition, five miRNAs (miR-128-3p, miR-130b-5p, miR-151a-5p, miR-330-3p, and miR-142-3p) were found to be more elevated in FA patients with diabetes.
The team noted that the “absence of diabetic controls prevents assessment of whether these changes were specific to [FA]-associated diabetes or reflect general diabetes-related dysregulation.”
“This study independently validates a circulating miRNA signature in [FA] and supports its value for hypertrophic cardiomyopathy risk stratification,” the researchers concluded. “Prospective, multi-center longitudinal studies will be crucial to advance these miRNA markers toward validated diagnostic tools and future integration into clinical guidelines.”
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