The pathogenesis of amyotrophic lateral sclerosis (ALS), a lethal neurodegenerative disease, remains undisclosed. Mutations in ALS related genes have been identified, albeit the majority of cases are unmutated. Clinical pathology of ALS suggests a prion-like cell-to-cell diffusion of the disease possibly mediated by exosomes, small endocytic vesicles involved in the propagation of RNA molecules and proteins. In this pilot study, we focused on exosomal microRNAs (miRNAs), key regulators of many signaling pathways. We analyzed serum-derived exosomes from ALS patients in comparison with healthy donors. Exosomes were obtained by a commercial kit. Purification of miRNAs was performed using spin column chromatography and RNA was reverse transcribed into cDNA. All samples were run on the miRCURY LNA^TM Universal RT miRNA PCR Serum/Plasma Focus panel. An average of 29 miRNAs were detectable per sample. The supervised analysis did not identify any statistically significant difference among the groups indicating that none of the miRNA of our panel has a strong pathological role in ALS. However, selecting samples with the highest miRNA content, six biological processes shared across miRNAs through the intersection of the GO categories were identified. Our results, combined to those reported in the literature, indicated that further investigation is needed to elucidate the role of exosome-derived miRNA in ALS.

The recent advances of quantum biology suggest a potential role in biomedical research. Studies related to electromagnetic fields, proton pumping in mitochondrial respiratory chain, quantum theory of T-cell receptor (TCR)-degeneracy, theories on biophotons, pyrophosphates or tubulin as possible carriers for neural information, and quantum properties of ions and protons, might be useful for understanding mechanisms of some serious immune, cardiovascular, and neural pathologies for which classic biomedical research, based on biochemical approach, is struggling to find new therapeutic strategies. A breakthrough in medical knowledge is therefore needed in order to improve the understanding of the complex interactions among various systems and organs typical of such pathologies. In particular, problems related to immune system over-activation, to the role of autonomic nervous system (ANS) dysfunction in the obstructive sleep apnea (OSA) syndrome, to the clinical consequences of ion channels dysfunction and inherited cardiac diseases, could benefit from the new perspective provided by quantum biology advancement. Overall, quantum biology might provide a promising biophysical theoretic system, on which to base pathophysiology understanding and hopefully therapeutic strategies. With the present work, authors hope to open a constructive and multidisciplinary debate on this important topic.

The most common genetic cause of Amyotrophic Lateral Sclerosis (ALS) is the expansion of a G4C2 hexanucleotide repeat in the C9orf72 gene. The size of the repeat expansion is highly variable and a cut-off of 30 repeats has been suggested as the lower pathological limit. Repeat size variability has been observed intergenerationally and intraindividually in tissues from different organs and within the same tissue, suggesting instability of the pathological repeat expansion. In order to study this genomic instability, we established iPSCs from five members of the same family of which four carried a C9orf72 repeat expansion and one was wild-type.