Clinical neurobiology

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Group leader:  Antonio Bertolotto

Clinical neurobiology

Projects

CReSM Bio-Bank
2015-2016 | FISM Italian Multiple Sclerosis Foundation

A bio-bank and a laboratory devoted to the collection and supply of biological samples of PPMS, the replication and sharing of data, and the validation of biological methods.
This project received the funds in April 2014 and, till now, in the CReSM biobank have been stored different biological materials (serum, plasma, DNA, total RNA, RNA from PBMCs and PBMCs in DMSO) from more than 2000 blood draws of Multiple Sclerosid and other neurological disease patients and from healthy controls.

Improving therapeutic appropriateness of Multiple Sclerosis treatments using biological approaches to personalize therapy and save pharmaceutical spending
2015-2018 | Italian Ministry of Health

The project aims to improve therapeutic appropriateness by using biological approaches, in particular:
•    early identification of biological non responders (NRs) to different approved treatments
•    better timing of drug administration, based on serum drug levels or specific drug biomarkers
•    study of the relationship, if any, between T-cells adhesion-molecule expression and the risk to develop serious adverse events during treatment.
This strategy can improve the efficacy of treatment, selecting the best drug for each patient, and save, or better allocate, enormous amounts of National Health System funds.

Evaluation of biological activity by RNA-sequencing in PEG-Interferon beta 1a and interferon beta 1a im treated multiple sclerosis patients and comparison of genetic expression between different cellular populations
2015-2016 | Biogen

This study is a pilot study that aims to evaluate biological activity in two groups of MS patients treated with Plegridy and Avonex respectively at different time points using the Next Generation Sequencing (NGS) technology. Data obtained from this pilot study can help to better understand IFNβ pharmacodynamic, which cellular subset is most influenced by treatment and the efficacy of treatment for every single patient

Combined analysis of EBV and cellular gene expression in clinically isolated syndrome, relapsing remitting and primary progressive multiple sclerosis: search of diagnostic and prognostic biomarkers
2015-2018 | FISM Italian Multiple Sclerosis Foundation

The hunt for biomarkers to predict MS disease evolution and identify patient subsets that may benefit from specific therapeutic regimens is a continuous effort in MS research. Because there is increasing evidence that EBV infection is strongly associated with MS and that the immune response to EBV differs both qualitatively and quantitatively in MS patients compared to healthy controls, a reasonable hypothesis to test is that EBV deregulation might be implicated in the dysimmune process that damages the CNS. From this it follows that combining the study of EBV infection status with that of the host’s immune system might help shed light into disease relevant virus-host interactions and identify biomarkers with predictive value.

The deubiquitinase A20/TNFAIP3 in the immunopathology of Multiple Sclerosis
2015-2018 | FISM/AISM

The enzyme A20 is s negative regulator of inflammation and immunity, which is associated to a genetic risk for MS and is deregulated in MS patients blood cells, particularly in monocytes. This study plans to deepen the role of A20 in monocytes, monocyte-derived cells and non-hematogenous brain-resident cells, in order to determine the involvement of the A20 altered expression in the pathogenesis of MS.

Regulatory cells: evaluation of the effect of IFN-beta treatment in MS patients
2015-2016 | Merck Serono    

Interferon beta (IFN-beta) is considered a broad spectrum therapeutic that holds the potential to restore the altered self-tolerance associated with MS pathogenesis, but its pleiotropic effects on immunity still not completely understood. This study aims at investigating the IFN-beta effect of on the full spectrum of regulatory cells, including T, B and NK regulatory cells, in patients with MS.

Diagnostic and prognostic biomarkers in multiple sclerosis: a possible role of Vitamin D Binding Protein isoforms
2014-2015 | FISM

Since MS is an heterogeneous and multifactor disease, the study of inter-individual differences in cerebrospinal fluid (CSF) proteome may contribute to the discovery of novel markers useful for diagnosis, disease subtype categorization and progression monitoring, as well as for the development of new therapeutic agents. Interestingly, in our previous FISM-founded project  (FISM 2007/R/10) we found that two isoforms of DBP were able to correctly subdivide patients on the basis of the disease clinical course in a follow-up of 5 years.
The aim of this project is to confirm and validate these preliminary proteomics data obtained from a blind proteomic analysis of CSF samples from an homogeneous population of patients. Moreover, in the previous study we highlighted an opposite trend of the values of the two spots corresponding to these different DBP isoforms, suggesting the involvement of a post-translational modification. Hence, in this study we aimed at identifying which post-translational modifications occurs in the differs in the two DBP isoforms.

The ubiquitin-editing enzyme A20 (TNFAIP3) as a peacekeeper in inflammation and immunity: a link between TNFAIP3 deregulation and Multiple Sclerosis
2012-2016 | Italian Ministry of Health

The enzyme A20 is a negative regulator of inflammation and immunity, which is associated to a genetic risk for MS and is deregulated in MS patients blood cells. This study plans to investigate the causes underlying the A20 deregulation in MS (genetic, epigenetic and hormonal), to compare the A20 expression in patients affected by different autoimmune diseases and to individuate  the immune cell populations mainly affected by the A20 expression deregulation in MS.