131 CLADIN: CLADribine and INnate immune responses. (29th July 2019)

• Record Type: Journal Article
• Authors: Monif, Mastura; Abdollahi, Shokoufeh; Stankovich, Jim; Maltby, Vicki; Lechner-Scott, Jeannette; Kalincik, Tomas; Hamilton, John; O'Brien, Terence; Butzkueven, Helmut
• Is Part Of: Journal of neurology, neurosurgery and psychiatry. Volume 90(2019)e7
• Page Start: A42
• Page End: A42
• Publication Date: 2019-07-29
• Subjects: Neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; Psychiatry -- Periodicals; 616.8
• DOI: 10.1136/jnnp-2019-anzan.116
• Languages: English
• ISSNs: 0022-3050

Abstract

Abstract : Introduction: Cladribine Tablets (Mavenclad®) is nucleoside analogue of deoxyadenosine, and an oral treatment for relapsing remitting MS (RRMS). In RRMS clinical trials, Cladribine has been shown to reduce brain atrophy, relapse rates, and new lesions on brain MRI. P2X7R is a purinergic receptor expressed in innate immune cells, and is thought to play a critical role in neuroinflammation. The mechanism of action of Cladribine on peripheral innate immune cells (monocytes), and its effect on P2X7R, is unclear, and forms the basis of this study. Methods: This will be a Phase IV, multi-centre, 3 year, translational trial. Patients who are starting Cladribine as part of their routine clinical care will consent to take part in the study. Monocyte numbers and activation states will be measured at various times prior and after commencement of therapy. In addition, and in an in vitro setting the effect of Cladribine on P2X7R expression and function will be assessed, as well as measuring various cytokines/chemokines in serum. The laboratory data will also be correlated with clinical data from another long-term Cladribine study, CLOBAS. Results: This study has been approved by Alfred Health Human Research Ethics Committee. The study is to commence in April 2019. Conclusion: This study will shed light on whether Cladribine is exerting its beneficial effects via action on peripheral monocytes and alterations of their P2X7Rs. The laboratory and clinical data will be analysed to understand the relationship between innate immune parameters and patient outcome.