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CLADIN- CLADribine and INnate immune response in multiple sclerosis - A phase IV prospective study.
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.
Affiliation
  • Monif M; Department of Neuroscience, Monash University, Melbourne, VIC, Australia; Department of Neurology, Melbourne Health, Melbourne, VIC, Australia; Department of Neurology, Alfred Health, Melbourne, VIC, Australia; Department of Physiology, The University of Melbourne, Melbourne, VIC, Australia. Electro
  • Sequeira RP; Department of Neuroscience, Monash University, Melbourne, VIC, Australia.
  • Muscat A; Department of Neuroscience, Monash University, Melbourne, VIC, Australia.
  • Stuckey S; Department of Neuroscience, Monash University, Melbourne, VIC, Australia.
  • Sanfilippo PG; Department of Neuroscience, Monash University, Melbourne, VIC, Australia.
  • Minh V; Department of Neurology, Alfred Health, Melbourne, VIC, Australia; School of Nursing, Midwifery and Paramedicine, Australian Catholic University, Melbourne, VIC, Australia.
  • Loftus N; Department of Neurology, Alfred Health, Melbourne, VIC, Australia.
  • Voo V; Department of Neuroscience, Monash University, Melbourne, VIC, Australia.
  • Fazzolari K; Department of Neurology, Melbourne Health, Melbourne, VIC, Australia.
  • Moss M; Department of Neurology, Alfred Health, Melbourne, VIC, Australia.
  • Maltby VE; John Hunter Hospital, Department of Neurology, New Lambton Heights, NSW, Australia; School of Medicine and Public Health, Hunter Medical Research Institute, University of Newcastle, Callaghan, NSW, Australia.
  • Nguyen AL; Department of Neurology, Melbourne Health, Melbourne, VIC, Australia; Department of Medicine, University of Melbourne, Melbourne, VIC, Australia.
  • Wesselingh R; Department of Neuroscience, Monash University, Melbourne, VIC, Australia; Department of Neurology, Alfred Health, Melbourne, VIC, Australia.
  • Seery N; Department of Neuroscience, Monash University, Melbourne, VIC, Australia; Department of Neurology, Alfred Health, Melbourne, VIC, Australia.
  • Nesbitt C; Department of Neurology, Alfred Health, Melbourne, VIC, Australia; Department of Neurology, Barwon Health, Melbourne, VIC, Australia.
  • Baker J; Department of Neurology, Alfred Health, Melbourne, VIC, Australia.
  • Dwyer C; Department of Neurology, Melbourne Health, Melbourne, VIC, Australia.
  • Taylor L; Department of Neurology, Melbourne Health, Melbourne, VIC, Australia.
  • Rath L; Department of Neurology, Alfred Health, Melbourne, VIC, Australia.
  • Van der Walt A; Department of Neuroscience, Monash University, Melbourne, VIC, Australia; Department of Neurology, Alfred Health, Melbourne, VIC, Australia.
  • Marriott M; Department of Neurology, Melbourne Health, Melbourne, VIC, Australia; Department of Medicine, University of Melbourne, Melbourne, VIC, Australia; Department of Neurology, Eastern Health, Melbourne, VIC, Australia.
  • Kalincik T; Department of Neurology, Melbourne Health, Melbourne, VIC, Australia; Department of Medicine, University of Melbourne, Melbourne, VIC, Australia.
  • Lechner-Scott J; John Hunter Hospital, Department of Neurology, New Lambton Heights, NSW, Australia; School of Medicine and Public Health, Hunter Medical Research Institute, University of Newcastle, Callaghan, NSW, Australia.
  • O'Brien TJ; Department of Neuroscience, Monash University, Melbourne, VIC, Australia; Department of Neurology, Alfred Health, Melbourne, VIC, Australia.
  • Butzkueven H; Department of Neuroscience, Monash University, Melbourne, VIC, Australia; Department of Neurology, Alfred Health, Melbourne, VIC, Australia.
Clin Immunol ; 265: 110304, 2024 Aug.
Article in En | MEDLINE | ID: mdl-38964633
ABSTRACT
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.
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Full text: 1 Database: MEDLINE Main subject: Monocytes / Cytokines / Cladribine / Multiple Sclerosis, Relapsing-Remitting / Immunity, Innate Limits: Adult / Female / Humans / Male / Middle aged Language: En Journal: Clin Immunol Journal subject: ALERGIA E IMUNOLOGIA Year: 2024 Type: Article
Fulltext
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Full text: 1 Database: MEDLINE Main subject: Monocytes / Cytokines / Cladribine / Multiple Sclerosis, Relapsing-Remitting / Immunity, Innate Limits: Adult / Female / Humans / Male / Middle aged Language: En Journal: Clin Immunol Journal subject: ALERGIA E IMUNOLOGIA Year: 2024 Type: Article