Biomarkers Of Disease Severity In Myotonic Dystrophy During Skeletal Muscle Rehabilitation (I11-4B)

OBJECTIVE: To develop microRNA as biomarkers of myotonic dystrophy (DM1) evolution during a rehabilitative protocol consisting of resistance training/Functional Electrical Stimulation (FES). BACKGROUND: DM1 is missing a circulating biomarkers ,we investigated serum and muscle microRNAs during a training program to reverse distal muscle atrophy and weakness in a group of genetically defined patients. MicroRNAs are short non-coding RNA molecules with single stranded sequence involved in many biological processes. There are some microRNAs expressed in muscle, particularly miR-1, miR-133a miR-133b, and miR-206(that was previously found by our group to be mislocalized in DM1 muscle, present in both cytoplasm and nucleus). DESIGN/METHODS: 12 DM1 muscle biopsies were scored for histopathological severity according to a graded severity score and microRNAs were investigated in muscle of these patients and in serum before and after an 8 week period of aerobic exercise and FES on leg muscle in a subset of 4 cases.DM1 patients underwent aerobic training and FES .We measured change from baseline value by 6MWT and muscle MRI. RESULTS: We found a decrease of miR-1, miR-133a and an increase in miR133b, and miR-206 in muscle. Before rehabilitation in 10 patients, in serum there was decrease of miR-1, miR-133b and miR-206 compared to control, whereas miR-133a showed increased levels. After our rehabilitation protocol, all four miRs analysed were significantly decreased. Patients showed increased 6-MWT (average 53 [percnt]) and reversed their muscle atrophy as documented by quantitative MRI. CONCLUSIONS: MiRNAs seem to be good biomarkers in sera of increased muscle mass, and correlate with muscle imaging and functional improvement MicroRNAs might bind to proteins connected with hypertrophy pathways or to regenerating myofibers. Taken together, there were several micro RNAs changes in sera that might be viable biomarkers .Aerobic training and FES seem to improve muscle function and strength in DM1.br />Study Supported by: AFM Disclosure: Dr. Angelini has received personal compensation for activities with Genzyme as an advisor. Dr. Fritegotto has nothing to disclose. Dr. Cudia has nothing to disclose.