This is a prospective non interventional study including patients with Relapsing-Remitting Multiple Sclerosis (RRMS) or with Neuromyelitis Optica Spectrum Disorders (NMOSD) and healthy subjects, who are enrolled within the routinely programmed clinical examinations at the IRCCS Neuromed (Pozzilli, Italy), IRCCS Polyclinic Hospital San Martino (Genoa, Italy) and Sant'Andrea Hospital - University of Rome La Sapienza (Rome, Italy). Specifically, the study investigates how ozanimod may contrast neurodegenerative mechanisms triggered by both arms of the adaptive immune response (T and B cells) and by their suboptimal regulation in MS. Overall, the project aims at assessing by in vitro experiments (there will be no patients on treatment with ozanimod and the drug will be only used in vitro): AIM1: ozanimod ability to modulate the synaptotoxic effect of T-cells derived from patients with MS relapse in a MS-chimeric ex-vivo model and to identify possible mediators (IRCCS Neuromed-Pozzilli, in collaboration with Synaptic Immunopathology Laboratory Dep. Systems Medicine, Tor Vergata University of Rome); AIM2: ozanimod ability to reduce the cytokine-mediated breakdown of the BBB and the migration of the here studied immune cells through ex vivo models of BBB (IRCCS Polyclinic Hospital San Martino); AIM3: ozanimod ability to affect the migration properties of Epstein Barr virus (EBV) infected B cells in MS (Sant'Andrea Hospital); AIM4: ozanimod ability to modulate the number and/or function of regulatory T cells (Treg), a lymphocyte population playing a key role in the control of pathogenic adaptive immune responses (Treg Cell Laboratory, Università degli Studi di Napoli "Federico II", Naples, Italy, receiving blood samples from Neuromed Hospital and Sant'Andrea Hospital; not recruiting unit). The work of the four labs is conceptually and operationally integrated: the labs at IRCCS Neuromed-Pozzilli/Tor Vergata University (Aim1) and at Polyclinic Hospital San Martino (Aim2) will investigate the effects of ozanimod on well-known mechanisms of damage in MS, inflammatory synaptopathy and BBB damage and immune cell migration. The lab at Sant'Andrea Hospital (Aim3), will verify whether B cells infected by different EBV genotypes are involved in BBB migration, and how ozanimod may interfere with this mechanism. The Treg Cell Laboratory (Aim4) will investigate whether ozanimod can also act "upstream" of these mechanisms by regulating the adaptive immune response.
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To evaluate the potential anti-synaptotoxic effect of ozanimod on electrophysiological kinetics in the MS chimeric model
Timeframe: 18 months
To evaluate the potential anti-synaptotoxic effect of ozanimod on electrophysiological frequency in the MS chimeric model
Timeframe: 18 months
To evaluate the potential anti-synaptotoxic effect of ozanimod on electrophysiological amplitude in the MS chimeric model
Timeframe: 18 months
To asses the ability of ozanimod to reduce the breakdown of the ex vivo model of BBB (BBB integrity).
Timeframe: 18 months
To asses the ability of ozanimod to reduce the cytokine-mediated permeability of the ex vivo model of BBB.
Timeframe: 18 months
To evaluate the migration properties of B cells, spLCLs (with 1.2 and with 1.3 viral alleles) and B95.8LCLs isolated from peripheral blood of (untreated) RRMS and HD.
Timeframe: 18 months
To evaluate the effect of ozanimod on the proliferation of Treg cells
Timeframe: 18 months
To evaluate the effect of ozanimod on metabolic asset of Treg cells.
Timeframe: 18 months
To evaluate the effect of ozanimod on the function of Treg cells.
Timeframe: 18 months