Amyotrophic Lateral Sclerosis: the role of a miRNA identified as a possible therapeutic target

A recent study published on the international journal Progress in neurobiology and carried out by the research group (Dr. Monica Nizzardo and Dr. Mafalda Rizzuti) headed by Prof. Stefania Corti (Centro Dino Ferrari, University of Milan, IRCCS Fondazione Ca’ Granda Ospedale Maggiore Policlinico), in collaboration with colleagues from the lab of Prof. Silvia Barabino (University Bicocca), investigated the role of a specific microRNA (miRNAs) as pathogenic factor and possible therapeutic target for Amyotrophic Lateral Sclerosis (ALS).

miRNAs are small non-coding RNAs that seem to be deeply involved in almost all biological processes. Several evidences support the importance of these molecules in the pathological mechanisms that underlie neurodegeneration. Indeed, since miRNAs are required for the survival of specific types of mature neurons in model organisms, they may play important roles in neurodegenerative disorders, such as ALS.

In this work, supported by ARISLA Foundation, the authors (first author Alessia Loffreda) identified high levels of miR-129-5p in different models of the disease and in peripheral blood cells of sporadic ALS patients. The increase of this miRNA causes the reduction of the protein ELAVL4/HuD which is predominantly expressed in neurons, where regulates neurite outgrowth and differentiation. Remarkably, the administration of an antisense oligonucleotide able to block miR-129-5p in a murine model of ALS, results in a significant increase in survival rate as well as amelioration of neuromuscular phenotype of treated transgenic rodents.

These data identify the potential role of miR-129-5p as promising therapeutic target that could be useful for developing new effective therapeutic approaches for ALS, suitable for being transferred into clinics.

Loffreda A, Nizzardo M, Arosio A, Ruepp MD, Calogero RA, Volinia S, Galasso M, Bendotti C, Ferrarese C, Lunetta C, Rizzuti M, Ronchi AE, Mühlemann O, Tremolizzo L, Corti S, Barabino SML. miR-129-5p: A key factor and therapeutic target in amyotrophic lateral sclerosis. Prog Neurobiol. 2020 Apr 24:101803. doi: 10.1016/j.pneurobio.2020.101803.