Analysis of microRNAs as novel biomarkers in Lysosomal Storage Diseases

Lysosomal storage disease (LSDs), including Pompe disease (PD) and Fabry disease (FD), represent a group of invalidating pathologies with a strong impact on patients' life expectancy. While remarkable progress in treatment has been made in recent years, the molecular mechanisms responsible for the phenotypic manifestations of these diseases and the key regulators of the functional pathways involved are still to be clarified. Given the increasing relevance conferred to small RNA molecules in human disease, also including neuromuscular disorders, we have studied the possible role of miRNA deregulation in PD and in FD. To globally characterize "disease-specific" miRNA expression profiles, we firsty applied a Next Generation Sequencing (NGS) approach, a new generation technology, quantitative and highly sensitive and more reliable if compared to hybridization-based methods. Identification of specific differentially espressed miRNAs (DE-miRNAs) in plasma and tissues/organs that are primary targets of disease in these LSDs may be exploited to develop novel therapeutic approaches and monitor disease progression. The analysis of miRNAs in these PD and FD represents a way to address some of the unmet medical needs: - Availability of markers of disease progression; - Markers of ERT efficacy; - Optimization of costs of therapies (ERT is highly expensive: 300.000-600.000 eu/year for a single patient); - Possible identification of novel therapeutic targets.