Obinutuzumab-Induced B Cell Depletion Reduces Spinal Cord Pathology in a CD20 Double Transgenic Mouse Model of Multiple Sclerosis

Autor: Stefanie Kuerten, Henrik Zetterberg, Verena Schropp, Eduard Urich, Sabine Tacke, Kaj Blennow, Thomas Breakell
Jazyk: angličtina
Rok vydání: 2020
Předmět:
obinutuzumab
Pathology
multiple sclerosis
lcsh:Chemistry
Myelin
Mice
Antineoplastic Agents
Immunological
Neurofilament Proteins
lcsh:QH301-705.5
Spectroscopy
CD20
B-Lymphocytes
biology
EAE
Experimental autoimmune encephalomyelitis
neurodegeneration
Antibodies
Monoclonal
General Medicine
Multiple Sclerosis
Chronic Progressive
Computer Science Applications
medicine.anatomical_structure
Spinal Cord
anti-CD20
Genetically modified mouse
medicine.medical_specialty
Encephalomyelitis
Autoimmune
Experimental
medicine.drug_class
Recombinant Fusion Proteins
Mice
Transgenic
Monoclonal antibody
Antibodies
Monoclonal
Humanized
Neuroprotection
Catalysis
Article
Inorganic Chemistry
medicine
Animals
ddc:610
Physical and Theoretical Chemistry
Remyelination
Myelin Proteolipid Protein
Molecular Biology
mAb
B cells
business.industry
Multiple sclerosis
Organic Chemistry
Myelin Basic Protein
medicine.disease
Antigens
CD20
Axons
Mice
Inbred C57BL
Disease Models
Animal
Microscopy
Electron
lcsh:Biology (General)
lcsh:QD1-999
Chronic Disease
biology.protein
business
Zdroj: International Journal of Molecular Sciences, Vol 21, Iss 6864, p 6864 (2020)
International Journal of Molecular Sciences
Volume 21
Issue 18
ISSN: 1661-6596
1422-0067
Popis: B cell-depleting therapies have recently proven to be clinically highly successful in the treatment of multiple sclerosis (MS). This study aimed to determine the effects of the novel type II anti-human CD20 (huCD20) monoclonal antibody (mAb) obinutuzumab (OBZ) on spinal cord degeneration in a B cell-dependent mouse model of MS. Double transgenic huCD20xHIGR3 (CD20dbtg) mice, which express human CD20, were immunised with the myelin fusion protein MP4 to induce experimental autoimmune encephalomyelitis (EAE). Both light and electron microscopy were used to assess myelination and axonal pathology in mice treated with OBZ during chronic EAE. Furthermore, the effects of the already established murine anti-CD20 antibody 18B12 were assessed in C57BL/6 wild-type (wt) mice. In both models (18B12/wt and OBZ/CD20dbtg) anti-CD20 treatment significantly diminished the extent of spinal cord pathology. While 18B12 treatment mainly reduced the extent of axonal pathology, a significant decrease in demyelination and increase in remyelination were additionally observed in OBZ-treated mice. Hence, the data suggest that OBZ could have neuroprotective effects on the CNS, setting the drug apart from the currently available type I anti-CD20 antibodies.
Databáze: OpenAIRE
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