CLADIN- CLADribine and INnate immune response in multiple sclerosis – A phase IV prospective study

Cladribine (Mavenclad®) is an oral treatment for relapsing remitting MS (RRMS), but its mechanism of action and its effects on innate immune responses in unknown. This study is a prospective Phase IV study of 41 patients with RRMS, and aims to investigate the mechanism of action of cladribine on per...

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Published in:Clinical immunology (Orlando, Fla.) Fla.), 2024-08, Vol.265, p.110304, Article 110304
Main Authors: Monif, Mastura, Sequeira, Richard P., Muscat, Andrea, Stuckey, Sian, Sanfilippo, Paul G., Minh, Viet, Loftus, Naomi, Voo, Veronica, Fazzolari, Katherine, Moss, Melinda, Maltby, Vicki E., Nguyen, Ai-Lan, Wesselingh, Robb, Seery, Nabil, Nesbitt, Cassie, Baker, Josephine, Dwyer, Chris, Taylor, Lisa, Rath, Louise, Van der Walt, Anneke, Marriott, Mark, Kalincik, Tomas, Lechner-Scott, Jeannette, O'Brien, Terence J., Butzkueven, Helmut
Format: Article
Language:English
Subjects:
Cladribine
Cytokines
Disease activity
Innate immunity
Monocytes
Multiple sclerosis
P2X7 receptor
Smouldering inflammation
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Summary:Cladribine (Mavenclad®) is an oral treatment for relapsing remitting MS (RRMS), but its mechanism of action and its effects on innate immune responses in unknown. This study is a prospective Phase IV study of 41 patients with RRMS, and aims to investigate the mechanism of action of cladribine on peripheral monocytes, and its impact on the P2X7 receptor. There was a significant reduction in monocyte count in vivo at week 1 post cladribine administration, and the subset of cells being most impacted were the CD14lo CD16+ ‘non-classical’ monocytes. Of the 14 cytokines measured in serum, CCL2 levels increased at week 1. In vitro, cladrabine induced a reduction in P2X7R pore as well as channel activity. This study demonstrates a novel mechanism of action for cladribine. It calls for studying potential benefits of cladribine in progressive forms of MS and other neurodegenerative diseases where innate immune related inflammation is implicated in disease pathogenesis.
ISSN:1521-6616
1521-7035
1521-7035
DOI:10.1016/j.clim.2024.110304