More than 100 microRNAs (miRs) are differentially expressed in the muscles of patients with spinal muscular atrophy (SMA), a new study by Italian researchers found. Three of these are significantly overexpressed in patients’ serum, suggesting they may be actively secreted by the skeletal muscles. 

According to the authors of the study published in eLife, these miRs could be used as prognostic biomarkers, even in presymptomatic patients. However, more research is needed to clarify their function and target cells.

With the development of new treatments for SMA, new prognostic biomarkers for the disease are urgently needed. Previous research has focused on the use of miRs as potential biomarkers in several conditions, including SMA.

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Here, a team of researchers led by Francesco Danilo Tiziano, MD, from the Department of Life Sciences and Public Health at Università Cattolica del Sacro Cuore in Rome, Italy performed a whole miRNome analysis of muscle samples obtained from patients with SMA and controls. They used 14 muscle biopsies and 9 muscle cultures to identify a possible disease signature and investigate the role of muscle tissue in the pathogenesis of SMA.

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They found that more than 100 miRs were differentially expressed in SMA muscles. They then assessed the levels of these miRs in the serum of patients and controls and found that 3 of them (HSA-miR-181a-5p, HSA-miR-324-5p, and HSA-miR-451) were upregulated in SMA patients’ serum.

When they integrated the levels of these 3 miRs in a composite SMA score with the transcript levels of the full-length SMN2 gene, SMN2 gene copy number, and age of the patient, they found that the phenotypic predictive value was markedly improved compared to SMN2 gene copy number alone.

The researchers stated, “The accuracy of the SMA-score needs to be verified in replicative studies.” They added, “If confirmed, it could be crucial for the routine prognostic assessment, also in presymptomatic patients.”

Currently, SMN2 gene copy number is the only consistent phenotypic modifier that is inversely correlated with SMA disease severity.

Reference

Abiusi E, Infante P, Cagnoli C, et al. SMA-miRs: miR-181a-5p, -324-5p, -451a are overexpressed in spinal muscular atrophy skeletal muscle and serum samples. eLife. Published online September 20, 2021. doi:10.7554/eLife.68054

MicroRNAs