Tel Aviv Medical Center

Author Of 1 Presentation

Disease Modifying Therapies – Mechanism of Action Poster Presentation

P0402 - Targeting monocyte migration for treatment of MS: Human ex-vivo proof-of-concept for Anti-MOSPD2 mAbs in patients with RR and progressive MS (ID 1067)

Speakers
Presentation Number
P0402
Presentation Topic
Disease Modifying Therapies – Mechanism of Action

Abstract

Background

In multiple sclerosis (MS), blood-borne monocytes constitute a part of the central nervous system (CNS)-infiltrating cells and are instrumental for disease pathogenesis. Therefore, inhibiting the migration of monocytes to the CNS could be a novel therapeutic approach for treatment of patients with MS and additional CNS inflammatory indications. MOSPD2 is a protein expressed on the surface of monocytes and is essential for their migration. We previously demonstrated that treatment with anti-MOSPD2 monoclonal antibodies (mAbs) prevented development and progression of experimental autoimmune encephalomyelitis (EAE) and restricted CNS-infiltration of monocytes.

Objectives

In this study, we tested the ability of anti-MOSPD2 mAbs to inhibit the migration of blood-borne monocytes isolated from relapsing-remitting (RRMS) primary progressive (PPMS) or secondary progressive MS (SPMS) patients.

Methods

Blood samples were drawn from RRMS, PPMS and SPMS patients. Isolated monocytes were tested for chemotaxis in the presence of two anti-MOSPD2 drug candidates, each binding a different epitope. Isotype control antibody was used as a reference.

Results

Twenty-five samples from RRMS, 4 from PPMS and 4 from SPMS patients were tested. At the time of sampling, patients were subscribed for treatment with various medications including dimethyl fumarate, natalizumab, cladribine, ocrelizumab, glatiramer acetate and interferon-beta. RRMS patients had an EDSS score at the range of 0-6. PPMS and SPMS patients had an EDSS score at the range of 5.5-6.5. Incubation with mAb1 and mAb2 profoundly inhibited migration of monocytes from all RRMS and progressive MS patients tested, by up to 97%. The ability to inhibit monocyte migration was not affected by patient subscribed medication for both RR and progressive MS.

Conclusions

Our data show that anti-MOSPD2 mAbs significantly inhibit the migration of monocytes isolated from MS patients in an ex-vivo setting, regardless of patient diagnosis, disease severity or treatment applied. Therefore, anti-MOSPD2 mAbs hold a therapeutic potential for RRMS and progressive MS, through a distinct mechanism of inhibiting monocyte accumulation in the CNS.

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