Abstract
Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disorder caused by out of frame mutations in the dystrophin gene. The hallmark symptoms of the condition include progressive degeneration of skeletal muscle, cardiomyopathy, and respiratory dysfunction. The most recent advances in therapeutic strategies for the treatment of DMD involve exon skipping or administration of minidystrophin, but these strategies are not yet universally available, nor have they proven to be a definitive cure for all DMD patients. Early diagnosis and tracking of symptom progression of DMD usually relies on creatine kinase tests, evaluation of patient performance in various ambulatory assessments, and detection of dystrophin from muscle biopsies, which are invasive and painful for the patient. While the current research focuses primarily on restoring functional dystrophin, accurate and minimally invasive methods to detect and track both symptom progression and the success of early DMD treatments are not yet available. In recent years, several groups have identified miRNA signature changes in DMD tissue samples, and a number of promising studies consistently detected changes in circulating miRNAs in blood samples of DMD patients. These results could potentially lead to non-invasive detection methods, new molecular approaches to treating DMD symptoms, and new methods to monitor of the efficacy of the therapy. In this review, we focus on the role of circulating miRNAs in DMD and highlight their potential both as a biomarker in the early detection of disease and as a therapeutic target in the prevention and treatment of DMD symptoms.
Highlights
MiRNAs are a class of short non-coding RNAs that function post-transcriptionally to regulate gene expression in a sequence-specific manner [1,2]. miRNA genes are located in clusters, transcribed with unique promoters, or found in intronic regions of protein-coding genes
This study finds that miR-29c-3p was significantly downregulated in the urine of Duchenne muscular dystrophy (DMD) patients that were still considered ambulatory, and that miR-23b-3p and miR-21-5p were both downregulated in the urine of non-ambulatory DMD patients [38]
There is an outstanding need for a highly sensitive and minimally invasive method to track symptom progression and whether or not a particular treatment is successful in improving these symptoms
Summary
MiRNAs are a class of short non-coding RNAs that function post-transcriptionally to regulate gene expression in a sequence-specific manner [1,2]. miRNA genes are located in clusters, transcribed with unique promoters, or found in intronic regions of protein-coding genes. Several decades of research have resulted in some experimental treatments that recently reached the clinical trial stage These approaches aim to treat DMD on a molecular basis, and include exon skipping therapy and the delivery of a shorter version of dystrophin (minidystrophin) [15]. Exon skipping approaches currently aim to bypass mutations located within this region, and it has been estimated that 40% of DMD patients, which do not possess mutation between these exons, would not directly benefit from this treatment [20] To overcome this obstacle, a recent study developed mutation-specific cocktails of antisense phosphorodiamidate morpholino oligomers targeting multiple exons [16]. These miRNAs have subsequently been named “dystromiRs.” They may be involved in cellular response to muscle damage and can potentially be exploited as highly specific biomarkers for each of these muscle disorders [31]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
