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http://hdl.handle.net/1942/32802
Title: | CNS delivery of anti-CD52 antibodies modestly reduces disease severity in an animal model for multiple sclerosis | Authors: | BOGIE, Jeroen GRAJCHEN, Elien WOUTERS, Elien BROUX, Bieke STINISSEN, Piet VAN WIJMEERSCH, Bart HENDRIKS, Jerome |
Issue Date: | 2020 | Publisher: | SAGE PUBLICATIONS LTD | Source: | THERAPEUTIC ADVANCES IN CHRONIC DISEASE, 11 (Art N° 2040622320947378) | Abstract: | Background and aims: Alemtuzumab is a humanized monoclonal antibody that depletes CD52-bearing B and T lymphocytes. Clinical trials defined that systemic administration of alemtuzumab reduces disease severity in the relapsing-remitting phase of multiple sclerosis (MS). However, its efficacy in progressive MS patients is limited, which may reflect the inability of alemtuzumab to cross the reconstituted BBB in these patients. Objective: to study whether central nervous system (CNS) delivery of anti-CD52 antibodies reduces disease severity and the neuroinflammatory burden in the experimental autoimmune encephalomyelitis (EAE) model. Methods: Anti-CD52 antibodies were administered intrathecally during the acute and chronic phases of EAE. Flow cytometry and immunohistochemistry were utilized to define immunological and pathological parameters. Results: We show that subcutaneously administrated anti-CD52 antibodies completely abolish EAE disease severity. CNS delivery of anti-CD52 antibodies during both the acute and chronic phases of EAE moderately reduces disease severity and the neuroinflammatory burden. Our findings further suggest that CNS delivery of anti-CD52 antibodies impacts both the peripheral and CNS immune cell compartments in the EAE model but not in healthy mice. Conclusion: Collectively, our findings highlight the therapeutic potential of CNS delivery of alemtuzumab for the treatment of progressive as well as early MS. | Notes: | Hendriks, JJA (corresponding author), Hasselt Univ, Biomed Res Inst, Dept Immunol & Infect, Agoralaan Bldg C, B-3590 Diepenbeek, Belgium. Jerome.hendriks@uhasselt.be |
Other: | Hendriks, JJA (corresponding author), Hasselt Univ, Biomed Res Inst, Dept Immunol & Infect, Agoralaan Bldg C, B-3590 Diepenbeek, Belgium. Jerome.hendriks@uhasselt.be | Keywords: | alemtuzumab;CD52;experimental autoimmune encephalomyelitis;lymphocytes;multiple sclerosis;neuroinflammation | Document URI: | http://hdl.handle.net/1942/32802 | ISSN: | 2040-6223 | e-ISSN: | 2040-6231 | DOI: | 10.1177/2040622320947378 | ISI #: | WOS:000563499600001 | Rights: | Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2021 |
Appears in Collections: | Research publications |
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2040622320947378.pdf | Published version | 1.53 MB | Adobe PDF | View/Open |
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