Indagini genetiche, molecolari e traslazionali in diverse forme di distrofie muscolari

The myotonic dystrophy (DM) is the most common form of muscular dystrophy in adults. In particular, an expansion of CTG triplet in the 3'UTR of the DMPK gene (myotonic dystrophy protein kinase) is responsible for myotonic dystrophy type 1 (DM1; MIM # 160900). DM1 is an autosomal dominant multisystemic desease, involving various systems of the human body such as the endocrine system, heart, skeletal muscle, eye and brain. It might present a congenital form, as well as the involvement of the central nervous system. MicroRNAs (miRNA) are short non coding RNA molecules with single stranded sequence, that can regulate gene expression at the post transcriptional level. They are involved in many biological processes such as embryonic development, differentiation and proliferation. There are some miRNAs expressed in the muscular tissue (myomiRs), in particular miR-1 and miR-133a/b, expressed in skeletal and cardiac muscle, and miR-206, expressed in skeletal muscle. The main objective is to study the expression profile of these miRNAs in skeletal muscle and serum of patients with myotonic dystrophy type 1. The results of the study in 12 biopsies shows a decrease of miR-1 and miR-133a in patients with DM1 compared with controls, while miR-133b doesn’t show significant changes, and miR-206 is significantly increased in the muscle of DM1 patients. These data were compared with the histopathological score of muscle biopsies of these patients. There was no correlation between alterations of miRNA expression and histopatological impairment of muscle. We analyzed the levels of miRNAs in the serum of patients DM1 before and after a period of 8 weeks of rehabilitation, to verify the role of these molecules and their involvement in muscle regeneration. At time zero (admission in hospital) there was a decrease in the expression of miR-1, miR-133b and miR-206 compared to controls, instead miR-133a showed increased level. After rehabilitation treatment (time one) there was a significant decrease of all four miRNAs analyze