MICRO-RNA AS NOVEL BIOMARKERS FOR LYSOSOMAL STORAGE DISEASES

The aim of the proposed project is to identify a set of novel biomarkers for PD and MPS IVA, and allow for more reliable and accurate assessment of patients clinical condition and outcome. We will analyze miRNA profile in plasma samples from patients affected by these two disorders by an NGS-based approach. To achieve this scope our approach is divided in the following scientific and technical objectives:

Specific Objective 1: to identify profiles of differentially expressed miRNAs in samples from PD patients.
After an exploratory study to validate the approach (see preliminary results) we will extend the analysis of miRNA expression levels in a larger cohort of PD patients. This analysis will provide us with a list of miRNAs that are differentially expressed in plasma from PD patients and profiles that are specific or associated to the disease. A bioinformatic analysis will be performed to identify the pathways in which the target genes of differentially expressed miRNAs are involved in order to gather information on the disease pathophysiology. We plan to analyze the miRNA profile in approximately 40-50 PD patients (both infantile onset and late-onset patients) and age-matched healthy controls.

Specific Objective 2:
to identify profiles of differentially expressed miRNAs in samples from MPS IVA patient. The specific aim 2 will be to extend the same studies and approach to another LSD, MPS IVA. Again we plan to identify miRNAs that are
differentially expresses in MPS IVA patients and profiles that are specific or associated to the disease. A bioinformatic analysis will be performed to identify the pathways in which the target genes of differentially expressed miRNAs are involved in order to gather information on the disease pathophysiology. We plan to analyze the miRNA profile in approximately 15 MPS IVA patients and age-matched healthy controls.

Specific Objective 3: to correlate the levels of dysregulated miRNAs and their profile with disease progression and with response to ERT. After obtainig specific miRNA expression profiles for each disorder we plan to correlate these profiles with age at onset, severity of phenoype, response to ERT, stage of disease progression. To this purpose we will collect a minimum data set of clinical information for both disorders and we will analyze correlations between clinical data and levels of individual or subsets of differentially expressed miRNA.