Diagnostic Circulating miRNAs in Sporadic Amyotrophic Lateral Sclerosis

Abstract

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by the neurodegeneration of motoneurons. About 10% of ALS is hereditary and involves mutation in 25 different genes, while 90% of the cases are sporadic forms of ALS (sALS). The diagnosis of ALS includes the detection of early symptoms and, as disease progresses, muscle twitching and then atrophy spreads from hands to other parts of the body. The disease causes high disability and has a high mortality rate; moreover, the therapeutic approaches for the pathology are not effective. miRNAs are small non-coding RNAs, whose activity has a major impact on the expression levels of coding mRNA. The literature identifies several miRNAs with diagnostic abilities on sALS, but a unique diagnostic profile is not defined. As miRNAs could be secreted, the identification of specific blood miRNAs with diagnostic ability for sALS could be helpful in the identification of the patients. In the view of personalized medicine, we performed a meta-analysis of the literature in order to select specific circulating miRNAs with diagnostic properties and, by bioinformatics approaches, we identified a panel of 10 miRNAs (miR-193b, miR-3911, miR-139-5p, miR-193b-1, miR-338-5p, miR-3911-1, miR-455-3p, miR-4687-5p, miR-4745-5p, and miR-4763-3p) able to classify sALS patients by blood analysis. Among them, the analysis of expression levels of the couple of blood miR-193b/miR-4745-5p could be translated in clinical practice for the diagnosis of sALS.

A Machine Learning Approach for Highlighting microRNAs as Biomarkers Linked to Amyotrophic Lateral Sclerosis Diagnosis and Progression

“…These discrepancies may result from different sampling, processing, and assay protocols used in different laboratories, or from the heterogeneous nature of ALS. Additional issues are the small sizes of the cohorts studied, the lack of investigation into the influence of lifestyle factors interfering with microRNA levels in the studied samples, and possible differences in ALS-related miRNA profiles due to the tissues/samples employed for the analysis, in agreement with what was observed by some authors [41]. From a reproducibility perspective, validation studies using independent datasets are essential for determining the utility of candidate miRNAs as robust biomarkers for ALS.…”

“…Considering that about 70% of miRNAs are expressed in the brain [39], it is not surprising that they can be promising biomarkers for ALS [40]. An increasing number of studies are currently focused on their possible use as non-invasive diagnostic biomarkers for ALS in a pre-symptomatic stage [41,42].…”

Biofluid Biomarkers in the Prognosis of Amyotrophic Lateral Sclerosis: Recent Developments and Therapeutic Applications

“…The main obstacles to date are the lack of consistency and overlap in specific ALS-associated miRNAs between the different study groups and a lack of longitudinal studies. In addition, interest has focused on the characterization of the circulating miRNA profile in ALS [ 86 , 87 ] and its diagnostic ability compared with that of other diseases and in controls. However, their prognostic performance has been explored less often.…”

Deregulation of Plasma microRNA Expression in a TARDBP-ALS Family

“…Several studies highlight the role of miRNA in ALS pathology by describing dysregulated miRNAs in various biological fluids (CSF, blood, plasma, and serum) in ALS patients compared to healthy controls [ 17 ]. It has been shown that miRNAs specifically produced in motor neurons are present in the plasma of ALS patients and are correlated with disease severity [ 18 ]. MiRNAs have several intrinsic characteristics that make them attractive as biomarkers.…”