Identificação de biomarcadores não invasivos para Distrofia Miotónica tipo 1

The identification of non-invasive molecular biomarkers for DM1 is particularly important for diagnosis, to monitor disease progression and effectiveness of new drug treatments in clinical trials. Given that DMPK is a serine/threonine protein kinase, whose reduced protein levels and activity in DM1 are well described, we hypothesize that protein phosphorylation is deregulated in DM1 (Fig.1) and that phosphoproteins are good biomarker candidates for DM1. Therefore, in this project, we intend to identify novel molecular biomarkers for DM1 by analyzing the proteome and phosphoproteome of DM1 patients’ dermal fibroblasts-, serum- and urine-derived extracellular vesicles (EVs) using a mass spectrometry approach. The specific objectives of this project are: 1. To characterize the DM1 UA (University of Aveiro) cohort of patients with DM1 1.1 To determine CTG expansion number in blood samples and dermal fibroblasts. 1.2 To characterize the cohort according to the patients’ age of onset, severity, progression and muscle strength and function. 2. To analyse the proteome and phosphoproteome of fibroblasts-, serum- and urine-derived EVs from DM1 patients 2.1 To identify the proteins and phosphoproteins deregulated in DM1 patients’ samples. 2.2 To establish the correlation between the identified biomarkers with DM1 patients’ phenotype. 3. To validate a unique signature of molecular biomarkers for DM1 3.1. To monitor the molecular biomarkers levels in DM1 animal models’ samples. 3.2. To monitor the molecular biomarkers levels in a larger panel of patients with DM1. 4. To manage the project and analyse, integrate and disseminate the results. The successful completion of the objectives will hopefully permit the identification of novel non-invasive biomarkers for DM1, in particular phosphoprotein-based biomarkers, which ultimately will impact patient’s care and improve their quality of life.