New biomarkers for a muscle disorder
The rare genetic disorder, myotonic dystrophy type 1 (DM1) or Steinert disease is clinically characterised by myotonia, muscle waste and heart conduction defects. Significant variability has been observed in the levels of the regulatory non-coding miRNA molecules in DM1, proposing it as a putative mechanism for the disease. Scientists on the EU-funded DM1-MIRNA (New therapeutic targets for DM1: miRNAs analysis in DM1 disease models) project investigated the role of altered miRNAs in different DM1 models and patient samples. The rationale was that this would help identify target genes and uncover the molecular mechanism of DM1 pathogenesis. Using the fruit fly Drosophila melanogaster as the model organism, researchers recapitulated the DM1 genetic environment and identified miRNA alterations in the disease state. The work focused on miRNA molecules that are highly conserved from flies to humans. A similar deregulation was observed in patient skin-muscle biopsies. Furthermore, an altered miRNA expression profile was discovered in DM1 patients' blood samples for the first time. An exhaustive study of several miRNAs circulating in human serum proved inconclusive for establishing a reliable DM1 miRNA biomarker. The high levels of heterogeneity found in the samples and utilised methodology might explain the inconclusive results. At the same time, positive results shown in recent publications from other research groups encourages a further search for non-invasive biomarkers for DM1. The project data in general has reinforced the translational nature and validity of the DM1-MIRNA project. Understanding how miRNAs are implicated in the DM1 phenotype could lead in the future to the discovery of novel biomarkers for diagnosis and monitoring of disease therapies.
Keywords
Micro RNAs, myotonic dystrophy type 1, DM1-MIRNA, Drosophila melanogaster, biomarker
