Therapeutic potential of anti-MOSPD2 monoclonal antibodies

Human proof-of-concept data showed that 2 monoclonal antibodies against motile sperm domain-containing protein 2 (MOSPD2) significantly inhibit the migration of monocytes from MS patients ex vivo, regardless of patient diagnosis, disease severity, or treatment applied [1]. Anti-MOSPD2 monoclonal antibodies, therefore, hold therapeutic potential for MS in all stages.

MOSPD2 is a surface protein expressed on monocytes and plays a key role in these cells’ ability to migrate to inflammatory sites, in a chemokine-agnostic manner. Study results of 2 anti-MOSPD2 monoclonal antibodies with distinct epitopes were presented.

Blood samples from 25 relapsing-remitting, 4 primary progressive, and 4 secondary-progressive MS patients were analysed. Isolated monocytes were tested for chemotaxis in the presence of 2 anti-MOSPD2 drug candidates, here referred to as mAb1 and mAb2. An isotype control antibody was used as a reference.

Incubation with mAb1 and mAb2 profoundly inhibited monocyte migration in all tested MS patients, by up to 97%. This effect was independent of disease stage, gender, and MS medication used. These human data provide, for the first time, proof of concept for the possibility to target monocyte migration in MS patients. This is a different mechanism from existing treatments (mostly targeting T and B cells), which helps explain that both anti-MOSPD2 monoclonal antibodies showed an additional efficacy to any therapy participants already used. The results indicate that this approach may be implemented in all types and stages of MS. A first-in-human study is planned for the second half of 2021.

1. Salem Y, et al. Targeting monocyte migration for treatment of MS: Human ex-vivo proof-of-concept for Anti-MOSPD2 mAbs in patients with RR and progressive MS. MSVirtual 2020, Abstract P0402.