Amyotrophic Lateral Sclerosis (ALS) is also known as motor neuron disease because it destroys the nerve cells that control voluntary muscle movement. It is a degenerative disease that progressively leads to paralysis and death of the patients within a few years of the clinical onset.

However, the course of the disease is not the same in all patients. Until now, the molecular basis for explaining it was unknown: many biomarkers have been described for various neurodegenerative diseases, but none of them displayed a specific correlation with ALS.

Now, the synergistic work of several clinical research centers, coordinated by Antonio Musarò and Irene Bozzoni, of Sapienza University of Rome and the Pasteur Institute-Italy laboratory, has led to the identification of potential prognostic biomarkers of ALS. They are small RNA molecules, namely microRNA (miRNA), which do not contain information for protein formation, but are often altered in certain pathological conditions and may also be released into the bloodstream.

In this study, published in Cell Death Discovery, five miRNAs were selected and quantitatively analysed every three months during disease progression. The results showed that these molecules appear to be predictive of disease progression. "Our study is the first to quantify the circulating levels of miRNAs in ALS patients during disease progression, thus allowing us to give a prognostic significance to three of the five molecules studied," says Antonio Musarò, "and it represents a basis from which to develop serological tests for the assessment of these molecules in ALS patients". 

"An excellent integration of expertise between research and clinic,' adds Irene Bozzoni.

"Quantifying the levels of these molecules", continues Musarò, "could be a valuable tool for the clinical management of these patients. The microRNAs we analysed represent indeed the molecular signature of ALS and provide an excellent tool to better define the aggressiveness and speed of disease progression and to use them to enroll patients more precisely in clinical trials.

The study was partially supported by the Fondazione Roma, ASI, ARiSLA, ERC, and the involved research centres' projects.

References:

A longitudinal study defined circulating microRNAs as reliable biomarkers for disease prognosis and progression in ALS human patients – Gabriella Dobrowolnyj, Julie Martone, Elisa Lepore, Irene Casola, Antonio Petrucci, Maurizio Inghilleri, Mariangela Morlando, Alessio Colantoni, Bianca Maria Scicchitano, Andrea Calvo, Giulia Bisogni, Adriano Chiò, Mario Sabatelli, Irene Bozzoni & Antonio Musarò – Cell Death Discovery, 2021. https://www.nature.com/articles/s41420-020-00397-6

Further Information

Antonio Musarò
Department of Anatomical Histological Medical Legal Sciences and Locomotor Apparatus
antonio.musaro@uniroma1.it