MicroRNA analysis in stem cells derived from ALS patients: towards new therapeutic strategies

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that affects a particular type of cells called motor neurons leading to progressive muscle weakness and atrophy. It is the most common and severe form of motor neuron disease in adults and death usually occurs within 3–5 years after diagnosis. Currently, due to the complexity of the disease there is no effective treatment and patients can rely only on supportive care and drugs which modestly prolong patients’ survival. The pathomechanism underlying the disease is largely unknown, even though increasing evidence suggests that RNA metabolism may play an important role.

A recent Italian study, published by the journal Scientific Reports (first author Dr. Mafalda Rizzuti), was conducted at the Neural Stem Cell Laboratory of the Dino Ferrari Center University of Milan, IRCCS Cà Granda Foundation, Ospedale Maggiore Policlinico. The group of researchers, led by Professor Stefania Corti, obtained progenitor motor neuronal cells differentiated from induced pluripotent stem cells (iPSCs) of ALS patients. iPSCs are obtained by reprogramming adult cells (i.e skin fibroblasts) in stem cells. The progenitor motor neurons represent a valid model for in vitro ALS studies, reproducing also the phase of motor neuron development and differentiation. The analysis of the expression profile of these cells has identified a subset of microRNAs that are less expressed in patients ‘ cells than control cells derived from healthy subjects. In particular, two identified microRNAs are linked with some of the degenerative processes responsible for the pathological mechanisms underlying the disease, representing new potential therapeutic targets.

Since a single miRNA is able to contemporaneously regulate many genes and pathways, modifying a single element can achieve a broader effect useful for a multifaceted disease such as ALS.

These results demonstrate that the ALS phenotype can be associated with a dysregulation of microRNAs involved in the control of neurodegeneration processes, suggesting that microRNA-based therapies may be an innovative therapeutic strategy to treat complex neurological diseases such as ALS.

-Rizzuti M, Filosa G, Melzi V, Calandriello L, Dioni L, Bollati V, Bresolin N,

Comi GP, Barabino S, Nizzardo M, Corti S. MicroRNA expression analysis identifies

a subset of downregulated miRNAs in ALS motor neuron progenitors. Sci Rep. 2018

Jul 4;8(1):10105. doi: 10.1038/s41598-018-28366-1. PubMed PMID: 29973608; PubMed

Central PMCID: PMC6031650.

https://www.nature.com/articles/s41598-018-28366-1