Details

Autor(en) / Beteiligte

• Coenen-Stass, Anna M.L.
• Wood, Matthew J.A.
• Roberts, Thomas C.

Titel

Biomarker Potential of Extracellular miRNAs in Duchenne Muscular Dystrophy

Ist Teil von

• Trends in molecular medicine, 2017-11, Vol.23 (11), p.989-1001

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• miRNAs are small, noncoding RNAs that not only regulate gene expression within cells, but might also constitute promising extracellular biomarkers for a variety of pathologies, including the progressive muscle-wasting disorder Duchenne Muscular Dystrophy (DMD). A set of muscle-enriched miRNAs, the myomiRs (miR-1, miR-133, and miR-206) are highly elevated in the serum of patients with DMD and in dystrophin-deficient animal models. Furthermore, circulating myomiRs might be used as pharmacodynamic biomarkers, given that their levels can be restored towards wild-type levels following exon skipping therapy in dystrophic mice. The relationship between muscle pathology and extracellular myomiR release is complex, and incompletely understood. Here, we discuss current progress leading towards the clinical utility of extracellular miRNAs as putative DMD biomarkers, and their possible contribution to muscle physiology. Extracellular myomiRs may be promising, minimally invasive biomarkers for the diagnosis of neuromuscular disorders, monitoring the progression of DMD pathology, and assessing the pharmacodynamic response following exon skipping therapy. Multiple factors contribute to ex-myomiR levels, including necrosis, regeneration, tissue expression levels, physical activity, and overall muscle mass, which complicate the interpretation of altered serum miRNA levels. The relationships between the therapeutic restoration of ex-myomiR levels and muscle function and/or patient benefit have yet to be demonstrated. Establishing such correlations is vital if ex-myomiRs are to be utilized as surrogate biomarkers in DMD clinical trials. Opinions vary widely as to the extent to which ex-miRNAs are biologically relevant, although several studies have suggested that ex-myomiRs act as intercellular signaling molecules that are transferred between cells in the muscle niche by extracellular vesicles.