Circulating microRNAs as biomarkers of muscle differentiation and atrophy in ALS.

Aims: The identification of circulating biomarkers is needed to facilitate diagnosis and prognosis of amyotrophic lateral sclerosis (ALS) and to offer indicators of therapeutic response in clinical trials. We aimed to investigate the levels of muscle-specific microRNAs in serum of ALS patients subdivided according to bulbar or spinal onset. Methods: In 14 ALS patients (10 spinal, 4 bulbar) we measured the serum levels of muscle-specific miR-206, miR-1, miR-133a/b, miR-27a, and the expression of myostatin and follistatin, which are negative regulators of muscle growth. Morphometric analysis of muscle fiber size was used to correlate muscle atrophy with biochemical-molecular parameters. Results: In ALS patients the expression of miR-206 and miR-133 was significantly increased and that of miR-27a was significantly reduced as compared to controls, and also between spinal vs. bulbar ALS. Myostatin/follistatin ratio was significantly higher in ALS than in controls and in bulbar versus spinal ALS. Bulbar ALS patients present higher degree of muscle atrophy than spinal ALS, as documented by our muscle fiber morphometric analysis. Conclusions: Muscle mass regulators are particularly down-expressed in bulbar ALS, suggesting a more rapid and diffuse atrophic process. These biomarkers may be considered as useful biochemical and molecular indicators involved both in neuromuscular junction maintenance and reinnervation process.