Panel of 6 microRNAs May Represent a Genetic Signature of Friedreich’s Ataxia, Study Suggests

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by Alice Melão |

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Increased levels of six small RNA molecules, or microRNAs, in the blood could be a specific genetic marker for Friedreich’s ataxia features and progression, researchers have found.

The study was titled “Differentially Regulated Cell-Free MicroRNAs in the Plasma of Friedreich’s Ataxia Patients and Their Association with Disease Pathology,” and was published in the journal Neuropediatrics.

Friedreich’s ataxia is an early-onset genetic disease that is characterized by progressive damage to the nerve cells. Initial symptoms are commonly associated with loss of muscular control and poor coordination. But with disease progression, patients often develop scoliosis, heart disease, and diabetes.

Until now no therapies were shown to effectively prevent or delay Friedreich’s ataxia progression. Still, several therapeutic strategies are under development with the hopes of improving patient care and outcome.

Like many other neurodegenerative diseases, researchers believe that an early diagnosis for Friedreich’s ataxia patients may improve a treatment’s chances of success. This underscores the need of measurements that can provide accurate information about a patient’s status.

A research team at the All India Institute of Medical Sciences in New Delhi, India, hypothesized that microRNA molecules could be potential biomarkers of Friedreich’s ataxia features.

MicroRNAs are small RNA molecules that can regulate the levels of gene-coding RNA sequences. Bioinformatics analyses have predicted that about 60 percent of all human genes are regulated by microRNA molecules.

This highlights their important role in normal cellular function as well as their potential involvement in disease development.

The team collected blood samples from 21 individuals with genetically confirmed Friedreich’s ataxia and from 21 healthy volunteers. They analyzed and compared the levels of microRNA in both groups.

They identified 17 microRNAs that were upregulated and three that were downregulated in the patients compared to the healthy controls. Analysis of the potential effects of these molecules revealed that they could potentially modulate the levels of about 1,800 genes.

A more detailed analysis showed that six specific microRNAs – identified as hsa-miR-15a-5p; hsa-miR-26a-5p; hsa-miR-29a-3p; hsa-miR-23a-3p; hsa-miR-223-3p; and hsa-24-3p – could regulate the levels of the enzymes DHFR, G6PT, and of the signaling factor BDNF.

This is of particular interest since these three molecules are involved in several mechanisms affected in Friedreich’s ataxia.

BDNF is a molecule that supports the growth, survival, and differentiation of nerve cells. A previous study showed that compounds that could mimic BDNF effects could also increase the levels of frataxin – the protein that is lacking in Friedreich’s ataxia – in nerve cells.

G6PT is an enzyme that has been linked to type 2 diabetes development, whereas DHFR is involved in folate metabolism and is linked to cellular survival and proliferation.

“The present study is expected to aid in the understanding of disease pathogenesis [disease development],” the researchers stated.

Overall, the researchers believe that the identified six microRNAs may be involved in several features associated with the development and progression of Friedreich’s ataxia.