The Laboratory performs both research and diagnostic activities.
Research activity: we mainly focus our research interests on Mucopolysaccharidoses (MPSs), a cluster of Lysosomal Storage Disorders, due to the deficit of the enzymes deputed to the degradation of mucopolysaccharides or glycosaminoglycans. Due to the deficit of lysosomal enzymes coded by housekeeping genes, MPSs generally affect most, if not all, organ-systems including brain in more than 70% of the cases. Although still not curable, in the last decade some MPSs have taken advantage by the availability of the Enzyme Replacement Therapy (ERT). The treatment, which has shown so far some peripheral efficacy, unfortunately does not help the CNS disease, due to the inability of the enzymes to cross the blood-brain barrier.
Main Projects of the Research Group
- In the last years, the Laboratory has been largely involved in the evaluation and application, in vitro and in vivo, of a Nanoparticle-based approach, functionalized to obtain drug brain-targeting, as a potential non-invasive therapeutic approach for MPS brain disease. We have successfully delivered Albumin, as a model high MW molecule, to the brain of MPS I and MPS II mouse models. We have also successfully delivered the recombinant form of the enzyme iduronate 2-sulfatase to the brain of the MPS II mouse model. We are presently optimizing the NPs-mediated strategy aiming at increasing enzyme stability and its encapsulated amount, though maintaining or even ameliorating the efficiency of delivery.
- With the aim to understand the onset of brain pathogenesis in these disorders, we are characterizing the brain parenchyma of the MPS II mouse model by evaluating different biomarkers at several progressive age of the animal, which will be also useful to monitor therapeutic efficacy of brain-targeted approaches at different animal ages.
- Our interest in the Bioinformatics and in the Personal Genomics fields is pursued by a project aimed at the development of new analytical systems for genomic and exomic data analysis and prioritization criteria in collaboration with the Department of Biology and the Biotechnology Center (CRIBI) of the University of Padua. In particular, we have focused our attention on the identification of potential gene modifiers, possibly to define the genotype-phenotype correlation in MPS VI. In this respect, we are also involved in the analysis of epigenetic determinants of Mucopolysaccharidoses.
- As for Advanced Diagnostics, we have recently set-up and validated a targeted panel for the contemporary molecular analysis of 50 Lysosomal Storage Disorders and we have very recently completed the “mutation update” of the ARSB gene, through a re-classification of all published variants, according to ACMG (American College of Medical Genetics and Genomics). This analysis, which we would like to extend to other genes of interest of our Group, is important to perform a correct molecular diagnosis.
Diagnostic activity: the laboratory also performs some biochemical and molecular analyses related to the diagnosis of Mucopolysaccharidoses.
- Francesca D’Avanzo
- Laura Rigon
- Alessandra Zanetti
- Concetta De Filippis
Selected PublicationsBertoldi L, Forcato C, Vitulo N, Birolo G, De Pascale F, Feltrin E, Schiavon R, Anglani F, Negrisolo S, Zanetti A, D'Avanzo F, Tomanin R, Faulkner G, Vezzi A, Valle G.. 2017. QueryOR: a comprehensive web platform for genetic variant analysis and prioritization.. BMC Bioinformatics, 18(1):225.
Salvalaio M, D'Avanzo F, Rigon L, Zanetti A, D'Angelo M, Valle G, Scarpa M, Tomanin R. . 2017. Brain RNA-Seq profiling of the Mucopolysaccharidosis type II mouse model. Int J Mol Sci, 17;18(5)
M Salvalaio, L Rigon, D Belletti, F D'Avanzo, F Pederzoli, B Ruozi, O Marin, MA Vandelli, F Forni, M Scarpa, R Tomanin, G Tosi.. 2016. Targeted Polymeric Nanoparticles for Brain Delivery of High Molecular Weight Molecules in Lysosomal Storage Disorders. PLoS One, 26;11(5):e0156452.
Zanetti A, Onenli-Mungan N, Elcioglu N, Ozbek MN, Kör D, Lenzini E, Scarpa M, Tomanin R.. 2014. Molecular Analysis of Turkish Maroteaux-Lamy Patients and Identification of One Novel Mutation in the Arylsulfatase B (ARSB) Gene.. Journal of Inherited Metabolic Disease Rep, 14:1-9
Tomanin R, Zanetti A, D Avanzo F, Rampazzo A, Gasparotto N, Parini R, Pascarella A, Concolino D, Procopio E, Fiumara A, Borgo A, Frigo A, Scarpa M.. 2014. Clinical efficacy of Enzyme Replacement Therapy in paediatric Hunter patients, an independent study of 3.5 years.. Orphanet J of Rare Dis, 18;9(1):129
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