FRRB Project 1734478 - Multiple sclerosis: translating alternative splicing events into therapeutic targets and biomarkers.


Name and Surname of PI

Elvezia Maria Paraboschi

Project Acronym


Project ID


Host Institution

Istituto Clinico Humanitas - Milan

Pathology of Interest

Multiple Sclerosis

Research Area

Autoimmune Diseases

Project Start Date

1 May 2021

Project End Date

30 April 2024


€ 600.000,00

Type of Project



Multiple sclerosis is an autoimmune neurodegenerative disease whose molecular mechanisms are not yet clear. The involvement of RNA metabolism and alternative splicing in its pathogenesis has however been suggested by studies showing an imbalance in RNAs produced by the splicing process in the context of the disease. The splicing is a fundamental mechanism for the cell, because it leads to the maturation of RNA molecules, essential for the production of proteins. The alternative splicing mechanism allows an increase of the number of RNAs and proteins produced starting from a single gene. Our hypothesis is that the dysregulation of alternative splicing and of another associated mechanism, the back-splicing process, leading to the formation of particular circular-shaped RNAs (circRNAs), could contribute to the pathogenesis of multiple sclerosis. In fact, an alteration of these mechanisms would lead to a change in the protein repertoire, which, in turn, could be involved in the neurodegeneration and autoimmunity features typical of the disease. The project studies the profiles of alternative splicing and circRNAs in the immune cells most involved in the disease, the lymphocytes, in patients affected by the disease and in healthy controls. The goal is to integrate these profiles with genetic and epigenetic information, deriving from DNA analysis, with the aim to understand their involvement in the pathogenesis of multiple sclerosis. Furthermore, alternative splicing and circRNA events, which are present in different amounts in patients compared to control subjects, could be used to develop biomarkers for the disease. This would allow for an easy-to-use, minimally invasive RNA-based diagnostic tool for the patient, which can complement traditional diagnostic methods.