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The Possible Neuroprotective Effect of Ocrelizumab Via VEGF Protein Expression in Relapsing Multiple Sclerosis Patients
Ocrelizumab (OCR) is a humanized anti-CD20 antibody approved for Relapsing Multiple Sclerosis (RMS) and Primary Progressive Multiple Sclerosis (PPMS), due to neuroprotective effects of partially unknown origin. While its mechanism of action is mainly thought to occur via B cell depletion, previous studies on rituximab, another anti-CD20 drug, showed that CD20 binding elicits several intracellular signalling pathways, also including Protein Kinase C (PKC) activation. Of interest, the β isoform of PKC is known to modulate, through the RNA-binding protein ELAV/HuR, the expression of Vascular Endothelial Growth Factor (VEGF), a signaling protein that has been suggested to play deleterious effects in the first phases of MS. Therefore, the hypothesis is that part of the neuroprotective effects exerted by OCR may also be due to the modulation of VEGF expression via PKCβ /HuR cascade. The primary objective is to evaluate the variation of the expression of VEGF (protein and mRNA) in Peripheral Blood Mononuclear Cells (PBMCs) induced by OCR therapy. No additional visits will be required outside of clinical practice. Additional laboratory testing (VEGF protein expression and PKCbeta/HuR cascade) will be performed on extra blood which will be taken during the routine blood exams. This study is an observational, longitudinal, monocenter and single arm study, in patients with RMS who are newly prescribed with OCR as per clinical practice. The study consists of the following visits as per clinical practice * T0 visit: at the first dose of OCR, blood sample and clinical/radiological MS data will be collected. * T6: after 6 months of OCR treatment, blood samples and clinical MS data will be collected. * T12 visit: after 12 months of OCR treatment, blood samples and clinical MS data will be collected.
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