MiRNAs, Myostatin, and Muscle MRI Imaging as Biomarkers of Clinical Features in Becker Muscular Dystrophy.

Becker muscular dystrophy (BMD) is an X-linked recessive disorder caused by dystrophin gene mutations. The phenotype and evolution of this muscle disorder are extremely clinical variable. In the last years, circulating biomarkers have acquired remarkable importance in their use as noninvasive biological indicators of prognosis and in monitoring muscle disease progression, especially when associated to muscle MRI imaging. We investigated the levels of circulating microRNAs (myo-miRNAs and inflammatory miRNAs) and of the proteins follistatin (FSTN) and myostatin (GDF-8) and compared results with clinical and radiological imaging data. In eight BMD patients, including two cases with evolving lower extremity weakness treated with deflazacort, we evaluated the expression level of 4 myo-miRNAs (miR-1, miR-206, miR-133a, and miR-133b), 3 inflammatory miRNAs (miR-146b, miR-155, and miR-221), FSTN, and GDF-8 proteins. In the two treated cases, there was pronounced posterior thigh and leg fibrofatty replacement assessed by muscle MRI by Mercuri score. The muscle-specific miR-206 was increased in all patients, and inflammatory miR-221 and miR-146b were variably elevated. A significant difference in myostatin expression was observed between steroid-treated and untreated patients. This study suggests that microRNAs and myostatin protein levels could be used to better understand the progression and management of the disease.